당신은 주제를 찾고 있습니까 “tumour cell invasion and migration diversity and escape mechanisms – Introduction to Cancer Biology (Part 3): Tissue Invasion and Metastasis“? 다음 카테고리의 웹사이트 https://chewathai27.com/you 에서 귀하의 모든 질문에 답변해 드립니다: https://chewathai27.com/you/blog. 바로 아래에서 답을 찾을 수 있습니다. 작성자 Mechanisms in Medicine 이(가) 작성한 기사에는 조회수 343,896회 및 좋아요 2,654개 개의 좋아요가 있습니다.
tumour cell invasion and migration diversity and escape mechanisms 주제에 대한 동영상 보기
여기에서 이 주제에 대한 비디오를 시청하십시오. 주의 깊게 살펴보고 읽고 있는 내용에 대한 피드백을 제공하세요!
d여기에서 Introduction to Cancer Biology (Part 3): Tissue Invasion and Metastasis – tumour cell invasion and migration diversity and escape mechanisms 주제에 대한 세부정보를 참조하세요
Another common mechanism of cancer biology is the ability of malignant cells to migrate from their original site to organs throughout the body. This animation provides a closer look at how the EGFR pathway activates and modulates this process of metastasis. This animation is the third part of the series \”An Introduction to Cancer Biology\”.
REFERENCES:
1. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell. 2000 Jan 7;100(1):57-70.
2. Herbst RS. Review of epidermal growth factor receptor biology. Int J Radiat Oncol Biol Phys. 2004;59(2 Suppl):21-6.
3. Gerharz CD, Ramp U, Reinecke P, et al. Analysis of growth factor-dependent signalling in human epithelioid sarcoma cell lines. Clues to the role of autocrine, juxtacrine and paracrine interactions in epithelioid sarcoma. Eur J Cancer. 2000 Jun;36(9):1171-9.
4. Potapova O, Fakhrai H, Mercola D. Growth factor PDGF-B/v-sis confers a tumorigenic phenotype to human tumor cells bearing PDGF receptors but not to cells devoid of receptors: evidence for an autocrine, but not a paracrine, mechanism. Int J Cancer. 1996 May 29;66(5):669-77.
5. Andl CD, Mizushima T, Nakagawa H, et al. Epidermal growth factor receptor mediates increased cell proliferation, migration, and aggregation in esophageal keratinocytes in vitro and in vivo. J Biol Chem. 2003 Jan 17;278(3):1824-30.
6. Di Fiore PP, Pierce JH, Kraus MH, Segatto O, King CR, Aaronson SA. erbB-2 is a potent oncogene when overexpressed in NIH/3T3 cells. Science. 1987 Jul 10;237(4811):178-82.
7. Batra SK, Castelino-Prabhu S, Wikstrand CJ, et al. Epidermal growth factor ligand-independent, unregulated, cell-transforming potential of a naturally occurring human mutant EGFRvIII gene. Cell Growth Differ. 1995 Oct;6(10):1251-9.
8. Egeblad M, Mortensen OH, Jaattela M. Truncated ErbB2 receptor enhances ErbB1 signaling and induces reversible, ERK-independent loss of epithelial morphology. Int J Cancer. 2001 Oct 15;94(2):185-91.
9. Lage A, Crombet T, González G. Targeting epidermal growth factor receptor signaling: early results and future trends in oncology. Ann Med. 2003; 35(5):327-36.
10. Adjei AA, Hidalgo M. Intracellular signal transduction pathway proteins as targets for cancer therapy. J Clin Oncol. 2005 Aug 10;23(23):5386-403.
11. Beeram M, Patnaik A, Rowinsky EK. Raf: a strategic target for therapeutic development against cancer. J Clin Oncol. 2005 Sep 20;23(27):6771-90.
12. Schmelzle T, Hall MN. TOR, a central controller of cell growth. Cell. 2000 Oct 13;103(2):253-62.
13. Yarden Y, Sliwkowski MX. Untangling the ErbB signalling network. Nat Rev Mol Cell Biol. 2001 Feb;2(2):127-37.
14. Igney FH, Krammer PH. Death and anti-death: tumour resistance to apoptosis. Nat Rev Cancer. 2002 Apr; 2(4):277-88.
15. Delhalle S, Duvoix A, Schnekenburger M, Morceau F, Dicato M, Diederich M. An introduction to the molecular mechanisms of apoptosis. Ann N Y Acad Sci. 2003 Dec;1010:1-8.
16. Veiby OP, Read MA. Chemoresistance: impact of nuclear factor (NF)-kappaB inhibition by small interfering RNA. Clin Cancer Res. 2004 May 15;10(10):3333-41.
17. Foo P. Metastasis: The journey of mobile cancer cells. Harvard Science Review. Spring 2002;30-2.
18. Hicklin DJ, Ellis LM. Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis. J Clin Oncol. 2005 Feb 10;23(5):1011-27.
19. Ellis LM. Epidermal growth factor receptor in tumor angiogenesis. Hematol Oncol Clin North Am. 2004 Oct; 18(5):1007-21.
20. Hurwitz H, Fehrenbacher L, Novotny W, et al. Bevacizumab plus Irinotecan, Fluorouracil, and Leucovorin for Metastatic Colorectal Cancer. N Engl J Med. 2004 Jun 3;350(23):2335-42.
21. Motzer RJ, Michaelson MD, Redman BG, et al. Activity of SU11248, a multitargeted inhibitor of vascular endothelial growth factor receptor and platelet-derived growth factor receptor, in patients with metastatic renal cell carcinoma. J Clin Oncol. 2006 Jan 1;24(1):16-24.
tumour cell invasion and migration diversity and escape mechanisms 주제에 대한 자세한 내용은 여기를 참조하세요.
Tumour-cell invasion and migration: diversity and escape …
Cancer cells possess a broad spectrum of migration and invasion mechanisms. These include both indivual and collective cell-migration strategies.
Source: pubmed.ncbi.nlm.nih.gov
Date Published: 12/9/2022
View: 7819
Tumour-cell invasion and migration: diversity and … – Nature
Cancer cells possess a broad spectrum of migration and invasion mechanisms. These include both indivual and collective cell-migration …
Source: www.nature.com
Date Published: 3/18/2022
View: 2039
Tumour-cell invasion and migration: Diversity and escape …
Cancer cells possess a broad spectrum of migration and invasion mechanisms. These include both indivual and collective cell-migration strategies.
Source: mdanderson.elsevierpure.com
Date Published: 1/20/2021
View: 5156
Tumour-cell invasion and migration: diversity and escape mechanisms
Key PointsThe process of tumour-cell invasion and metastasis is conventionally understood as the migration of indivual cells that detach from the primary …
Source: app.dimensions.ai
Date Published: 11/2/2021
View: 6912
Tumour-cell invasion and migration … – Semantic Scholar
Cancer cells possess a broad spectrum of migration and invasion mechanisms and learning more about the cellular and molecular basis of these …
Source: www.semanticscholar.org
Date Published: 10/18/2021
View: 9591
Tumour-cell invasion and migration: diversity and escape …
ISSN: 1474-175X , 1474-1768 ,. , Nature reviews. , 2003, Vol.3(5), p.362-374 ,. Tumour-cell invasion and migration: diversity and escape mechanisms.
Source: library-collections-search.westminster.ac.uk
Date Published: 2/12/2022
View: 1936
Tumour-cell invasion and migration – UTS Library
Tumour-cell invasion and migration: diversity and escape mechanisms.-article.
Source: search.lib.uts.edu.au
Date Published: 12/16/2021
View: 5285
주제와 관련된 이미지 tumour cell invasion and migration diversity and escape mechanisms
주제와 관련된 더 많은 사진을 참조하십시오 Introduction to Cancer Biology (Part 3): Tissue Invasion and Metastasis. 댓글에서 더 많은 관련 이미지를 보거나 필요한 경우 더 많은 관련 기사를 볼 수 있습니다.
주제에 대한 기사 평가 tumour cell invasion and migration diversity and escape mechanisms
- Author: Mechanisms in Medicine
- Views: 조회수 343,896회
- Likes: 좋아요 2,654개
- Date Published: 2012. 10. 27.
- Video Url link: https://www.youtube.com/watch?v=bdWRZd19swg
What is cell invasion and migration?
The process of tumour-cell invasion and metastasis is conventionally understood as the migration of individual cells that detach from the primary tumour, enter lymphatic vessels or the bloodstream and seed in distant organs.
How do cancer cells migrate?
Cancer cells can disseminate via amoeboid cell migration, mesenchymal cell migration or collective cell migration. Tumor microenvironment and certain therapeutic challenge can trigger the transitions of migration patterns. Plasticity of cancer cells migration limit efficiency of anti-metastasis therapies.
What is cancer cell invasion?
Invasion refers to the direct extension and penetration by cancer cells into neighbouring tissues. The proliferation of transformed cells and the progressive increase in tumour size eventually leads to a breach in the barriers between tissues, leading to tumour extension into adjacent tissue.
What causes cell migration?
Cells often migrate in response to specific external signals, including chemical signals and mechanical signals. Errors during this process have serious consequences, including intellectual disability, vascular disease, tumor formation and metastasis.
What is the difference between migration and invasion assay?
Definition. Migration assay refers to the methods involved in the determination of cell movement due to a particular stimulus while invasion assay refers to the methods involved in the determination of cell movement through the extracellular matrix. Thus, this is the main difference between migration and invasion assay …
What is migration in cells?
Cell migration is an evolutionarily conserved, multifaceted process which allows individual cells and cell groups to move, change position and build, or maintain tissues and organs for embryonic development as well as homeostasis and regeneration (Sonnemann & Bement, 2011; From: Advances in Cancer Research, 2016.
Why is cell migration important in cancer pathology?
Cancer-cell migration is critical for distant metastases. The cell’s ability to rearrange its cytoskeleton and propel itself forward is necessary before invasion and movement throughout various tissues can occur. Cells that cannot move towards a source of nutrition (blood vessels, for instance) will likely not survive.
What are 3 ways cancer can spread?
There are three primary ways tumors can spread to distant organs: Through the circulatory (blood) system (hematogenous) Through the lymphatic system. Through the body wall into the abdominal and chest cavities (transcoelomic).
What is the difference between invasion and metastasis?
Tissue invasion is the mechanism by which tumor cells expand into nearby environments. Metastasis refers to the process of tumor cells breaking away from the primary tumor, migrating to a new location and establishing a new, or secondary tumor, in the new environment.
Which tumor has power to invade and migrate?
Metastatic tumor cells go through stages of detachment from the primary tumor sites, invasion into circulation, extravasation into the appropriate secondary site, and establishment of a microenvironment supporting their energetic requirements.
How do cancer cells escape from their tissue of origin?
Tumor cells acquire genetic and epigenetic lesions that promote escape from their tissue of origin. Remodeling of the native tissue and formation of aberrant tumor vasculature facilitates tumor cell escape.
Do cancer cells migrate in groups?
Metastasis begins with the invasion of tumor cells into the stroma and migration toward the blood stream. Human pathology studies suggest that tumor cells invade collectively as strands, cords and clusters of cells into the stroma, which is dramatically reorganized during cancer progression.
What are the two types of cell migration?
Roughly speaking, cell migration can be categorized into single-cell migration and collective cell migration. Each migration mode is then further sub-categorized into several different types of migration (Figure 1). Next to migration, cells can also display invasion.
What are the steps in cell migration?
At the level of the light microscope, the cycle can be divided into five steps: (1) extension of the leading edge; (2) adhesion to matrix contacts; (3) contraction of the cytoplasm; (4) release from contact sites; and (5) recycling of membrane receptors from the rear to the front of the cell.
When does cell migration occur?
In a developing embryo, cell migration is the driving factor for various morphogenetic events. For instance, during gastrulation in very early embryos, groups of cells migrate as sheets to form the three germ layers.
How do you study cell migration?
The speed of wound closure and cell migration can be quantified by taking snapshot pictures with a regular inverted microscope at several time intervals. More detailed cell migratory behavior can be documented using the time-lapse microscopy system.
Can humans migrate?
Human migration is the movement of people from one place in the world to another. Human patterns of movement reflect the conditions of a changing world and impact the cultural landscapes of both the places people leave and the places they settle.
What is Matrigel used for?
Matrigel has been used in various in vitro assays for angiogenesis, cell invasion, spheroid formation, organoid formation from a single cell, etc. In vivo Matrigel improves/promotes tumor xenograft growth and is used to measure angiogenesis, improve heart and spinal cord repair, increase tissue transplant take, etc.
What cells can proliferate?
Stem cells undergo cell proliferation to produce proliferating “transit amplifying” daughter cells that later differentiate to construct tissues during normal development and tissue growth, during tissue regeneration after damage, or in cancer.
WWW Error Blocked Diagnostic
Access Denied
Your access to the NCBI website at www.ncbi.nlm.nih.gov has been temporarily blocked due to a possible misuse/abuse situation involving your site. This is not an indication of a security issue such as a virus or attack. It could be something as simple as a run away script or learning how to better use E-utilities, http://www.ncbi.nlm.nih.gov/books/NBK25497/, for more efficient work such that your work does not impact the ability of other researchers to also use our site. To restore access and understand how to better interact with our site to avoid this in the future, please have your system administrator contact [email protected].
Tumour-cell invasion and migration: diversity and escape mechanisms
Chambers, A. F., Groom, A. C. & MacDonald, I. C. Dissemination and growth of cancer cells in metastatic sites. Nature Rev. Cancer 2, 563–572 (2002).
Friedl, P. & Bröcker, E. -B. The biology of cell locomotion within three-dimensional extracellular matrix. Cell. Mol. Life Sci. 57, 41–64 (2000).
Abercrombie, M., Dunn, G. A. & Heath, J. P. The shape and movement of fibroblasts in culture. Soc. Gen. Physiol. Ser. 32, 57–70 (1977).
Lauffenburger, D. A. & Horwitz, A. F. Cell migration: a physically integrated molecular process. Cell 84, 359–369 (1996). The ‘bible’ for cell migration researchers.
Adams, J. C. Cell-matrix contact structures. Cell. Mol. Life Sci. 58, 371–392 (2001).
Burridge, K. & Chrzanowska-Wodicka, M. Focal adhesions, contractility, and signaling. Annu. Rev. Cell Dev. Biol. 12, 463–519 (1996).
Cramer, L. P. Organization and polarity of actin filament networks in cells: implications for the mechanism of myosin-based cell motility. Biochem. Soc. Symp. 65, 173–205 (1999).
Rohatgi, R. et al. The interaction between N-WASP and the Arp2/3 complex links Cdc42-dependent signals to actin assembly. Cell 97, 221–231 (1999).
Hynes, R. O. Integrins: bidirectional, allosteric signaling machines. Cell 110, 673–687 (2002).
Otey, C. A. & Burridge, K. Patterning of the membrane cytoskeleton by the extracellular matrix. Semin. Cell Biol. 1, 391–399 (1990).
Zamir, E. et al. Dynamics and segregation of cell-matrix adhesions in cultured fibroblasts. Nature Cell Biol. 2, 191–196 (2000).
Zamir, E. & Geiger, B. Molecular complexity and dynamics of cell-matrix adhesions. J. Cell Sci. 114, 3583–3590 (2001). References 11 and 12 explain the dynamic nature and diversity of cell-matrix interactions. They provide the molecular basis for plasticity and adaptation responses in cell migration.
Regen, C. M. & Horwitz, A. F. Dynamics of beta 1 integrin-mediated adhesive contacts in motile fibroblasts. J. Cell Biol. 119, 1347–1359 (1992).
Smilenov, L. B., Mikhailov, A., Pelham, R. J., Marcantonio, E. E. & Gundersen, G. G. Focal adhesion motility revealed in stationary fibroblasts. Science 286, 1172–1174 (1999).
Cukierman, E., Pankov, R., Stevens, D. R. & Yamada, K. M. Taking cell-matrix adhesions to the third dimension. Science 294, 1708–1712 (2001).
Rabinovitz, I. & Mercurio, A. M. The integrin alpha6beta4 functions in carcinoma cell migration on laminin-1 by mediating the formation and stabilization of actin-containing motility structures. J. Cell Biol. 139, 1873–1884 (1997).
Leavesley, D. I., Ferguson, G. D., Wayner, E. A. & Cheresh, D. A. Requirement of the integrin beta 3 subunit for carcinoma cell spreading or migration on vitronectin and fibrinogen. J. Cell Biol. 117, 1101–1107 (1992).
Maaser, K. et al. Functional hierarchy of simultaneously expressed adhesion receptors: integrin alpha2beta1 but not CD44 mediates MV3 melanoma cell migration and matrix reorganization within three-dimensional hyaluronan-containing collagen matrices. Mol. Biol. Cell 10, 3067–3079 (1999).
Friedl, P. et al. Migration of highly aggressive MV3 melanoma cells in 3-dimensional collagen lattices results in local matrix reorganization and shedding of alpha2 and beta1 integrins and CD44. Cancer Res. 57, 2061–2070 (1997).
Friedl, P. & Wolf, K. Proteolytic and non–proteolytic migration in tumor cells and leukocytes. Biochem. Soc. Symp. (in the press).
Byers, H. R. & Fujiwara, K. Stress fibers in cells in situ: immunofluorescence visualization with antiactin, antimyosin, and anti-alpha-actinin. J. Cell Biol. 93, 804–811 (1982).
Katoh, K. et al. Rho-kinase-mediated contraction of isolated stress fibers. J. Cell Biol. 153, 569–584 (2001).
Chew, T. L., Wolf, W. A., Gallagher, P. J., Matsumura, F. & Chisholm, R. L. A fluorescent resonant energy transfer-based biosensor reveals transient and regional myosin light chain kinase activation in lamella and cleavage furrows. J. Cell Biol. 156, 543–553 (2002).
Kaibuchi, K., Kuroda, S. & Amano, M. Regulation of the cytoskeleton and cell adhesion by the Rho family GTPases in mammalian cells. Annu. Rev. Biochem. 68, 459–486 (1999).
Totsukawa, G. et al. Distinct roles of ROCK (Rho-kinase) and MLCK in spatial regulation of MLC phosphorylation for assembly of stress fibers and focal adhesions in 3T3 fibroblasts. J. Cell Biol. 150, 797–806 (2000).
Kamm, K. E. & Stull, J. T. Dedicated myosin light chain kinases with diverse cellular functions. J. Biol. Chem. 276, 4527–4530 (2001).
Somlyo, A. V. et al. Rho kinase and matrix metalloproteinase inhibitors cooperate to inhibit angiogenesis and growth of human prostate cancer xenotransplants. FASEB J. 17, 223–234 (2003).
Verkhovsky, A. B., Svitkina, T. M. & Borisy, G. G. Myosin II filament assemblies in the active lamella of fibroblasts: their morphogenesis and role in the formation of actin filament bundles. J. Cell Biol. 131, 989–1002 (1995).
Friedl, P. & Brocker, E. B. in Image Analysis. Methods and Applications 2nd edn (ed. Hader, D. P.) 9–21 (CRC Press, London, 2001).
Palecek, S. P., Loftus, J. C., Ginsberg, M. H., Lauffenburger, D. A. & Horwitz, A. F. Integrin-ligand binding properties govern cell migration speed through cell-substratum adhesiveness. Nature 385, 537–540 (1997).
Ballestrem, C., Hinz, B., Imhof, B. A. & Wehrle-Haller, B. Marching at the front and dragging behind: differential alphaVbeta3-integrin turnover regulates focal adhesion behavior. J. Cell Biol. 155, 1319–1332 (2001).
Potter, D. A. et al. Calpain regulates actin remodeling during cell spreading. J. Cell Biol. 141, 647–662 (1998).
Friedl, P., Zanker, K. S. & Bröcker, E. -B. Cell migration strategies in 3-D extracellular matrix: differences in morphology, cell matrix interactions, and integrin function. Microsc. Res. Tech. 43, 369–378 (1998).
Entschladen, F., Niggemann, B., Zänker, K. S. & Friedl, P. Differential requirement of protein tyrosine kinases and protein kinase C in the regulation of T cell locomotion in three-dimensional collagen matrices. J. Immunol. 159, 3203–3210 (1997).
Friedl, P., Entschladen, F., Conrad, C., Niggemann, B. & Zanker, K. S. CD4+ T lymphocytes migrating in three-dimensional collagen lattices lack focal adhesions and utilize beta1 integrin-independent strategies for polarization, interaction with collagen fibers and locomotion. Eur. J. Immunol. 28, 2331–2343 (1998).
Yamada, K. M. et al. Monoclonal antibody and synthetic peptide inhibitors of human tumor cell migration. Cancer Res. 50, 4485–4496 (1990).
Filardo, E. J., Brooks, P. C., Deming, S. L., Damsky, C. & Cheresh, D. A. Requirement of the NPXY motif in the integrin beta 3 subunit cytoplasmic tail for melanoma cell migration in vitro and in vivo. J. Cell Biol. 130, 441–450 (1995).
Flanagan, L. A. et al. Filamin A, the Arp2/3 complex, and the morphology and function of cortical actin filaments in human melanoma cells. J. Cell Biol. 155, 511–517 (2001).
Sameni, M., Moin, K. & Sloane, B. F. Imaging proteolysis by living human breast cancer cells. Neoplasia 2, 496–504 (2001).
Rosenthal, E. L., Hotary, K., Bradford, C. & Weiss, S. J. Role of membrane type 1-matrix metalloproteinase and gelatinase A in head and neck squamous cell carcinoma invasion in vitro. Otolaryngol. Head Neck Surg. 121, 337–343 (1999).
Koblinski, J. E., Ahram, M. & Sloane, B. F. Unraveling the role of proteases in cancer. Clin. Chim. Acta 291, 113–135 (2000).
Hofmann, U. B., Westphal, J. R., van Muijen, G. N. & Ruiter, D. J. Matrix metalloproteinases in human melanoma. J. Invest. Dermatol. 115, 337–344 (2000).
Deryugina, E. I., Bourdon, M. A., Reisfeld, R. A. & Strongin, A. Remodeling of collagen matrix by human tumor cells requires activation and cell surface association of matrix metalloproteinase-2. Cancer Res. 58, 3743–3750 (1998).
Maekawa, K., Sato, H., Furukawa, M. & Yoshizaki, T. Inhibition of cervical lymph node metastasis by marimastat (BB-2516) in an orthotopic oral squamous cell carcinoma implantation model. Clin. Exp. Metastasis 19, 513–518 (2002).
Rudolph-Owen, L. A., Chan, R., Muller, W. J. & Matrisian, L. M. The matrix metalloproteinase matrilysin influences early-stage mammary tumorigenesis. Cancer Res. 58, 5500–5506 (1998).
Sahai, E., Olson, M. F. & Marshall, C. J. Cross-talk between Ras and Rho signalling pathways in transformation favours proliferation and increased motility. EMBO J. 20, 755–766 (2001).
Clark, E. A., Golub, T. R., Lander, E. S. & Hynes, R. O. Genomic analysis of metastasis reveals an essential role for RhoC. Nature 406, 532–535 (2000).
Itoh, K. et al. An essential part for Rho-associated kinase in the transcellular invasion of tumor cells. Nature Med. 5, 221–225 (1999).
Kaneko, K., Satoh, K., Masamune, A., Satoh, A. & Shimosegawa, T. Myosin light chain kinase inhibitors can block invasion and adhesion of human pancreatic cancer cell lines. Pancreas 24, 34–41 (2002).
Allman, R., Cowburn, P. & Mason, M. In vitro and in vivo effects of a cyclic peptide with affinity for the alpha(nu)beta3 integrin in human melanoma cells. Eur. J. Cancer 36, 410–422 (2000).
Gianelli, G., Falk-Marzillier, J., Schiraldi, O., Stetler-Stevenson, W. G. & Quaranta, V. Induction of cell migration by matrix metalloprotease-2 cleavage of laminin-5. Science 277, 225–228 (1997).
Alper, O. et al. Epidermal growth factor receptor signaling and the invasive phenotype of ovarian carcinoma cells. J. Natl Cancer Inst. 93, 1375–1384 (2001).
Seftor, R. E. et al. Cooperative interactions of laminin 5 gamma2 chain, matrix metalloproteinase-2, and membrane type-1-matrix/metalloproteinase are required for mimicry of embryonic vasculogenesis by aggressive melanoma. Cancer Res. 61, 6322–6327 (2001).
Brooks, P. C. et al. Insulin-like growth factor receptor cooperates with integrin alpha v beta 5 to promote tumor cell dissemination in vivo. J. Clin. Invest. 99, 1390–1398 (1997).
Thiery, J. P. Epithelial–mesenchymal transitions in tumour progression. Nature Rev. Cancer 2, 442–454 (2002). Comprehensive review on a classic example of plasticity during tumour invasion.
Enterline, H. T. & Cohen, D. R. The ameboid motility of human and animal neoplastic cells. Cancer 3, 1033–1038 (1950).
Wood, S. Jr. Pathogenesis of metastasis formation observed in vivo in the rabbit ear chamber. Arch. Pathol. 66, 550–568 (1958).
Wolf, K. et al. Compensation mechanism in tumor cell migration: mesenchymal–amoeboid transition after blocking of pericellular proteolysis. J. Cell Biol. 160, 267–277 (2003). A novel escape mechanism after the blocking of pericellular proteolysis. By converting to a more ‘primitive’ amoeboid migration mode, previously proteolytic tumour cells continue to move non-proteolytically by path-finding migration strategies.
Paulus, W., Baur, I., Beutler, A. S. & Reeves, S. A. Diffuse brain invasion of glioma cells requires beta 1 integrins. Lab. Invest. 75, 819–826 (1996).
Polette, M. et al. Association of fibroblastoid features with the invasive phenotype in human bronchial cancer cell lines. Clin. Exp. Metastasis 16, 105–112 (1998).
Tester, A. M., Ruangpani, N., Anderso, R. L. & Thompson, E. W. MMP-9 secretion and MMP-2 activation distinguish invasive and metastatic sublines of a mouse mammary carcinoma system showing epithelial–mesenchymal transition traits. Clin. Exp. Metastasis 18, 553–560 (2000).
Putz, E. et al. Phenotypic characteristics of cell lines derived from disseminated cancer cells in bone marrow of patients with solid epithelial tumors: establishment of working models for human micrometastases. Cancer Res. 59, 241–248 (1999).
d’Ortho, M. P. et al. MT1-MMP on the cell surface causes focal degradation of gelatin films. FEBS Lett. 421, 159–164 (1998).
Jeffers, M., Rong, S. & Vande, W. G. Enhanced tumorigenicity and invasion-metastasis by hepatocyte growth factor/scatter factor-Met signalling in human cells concomitant with induction of the urokinase proteolysis network. Mol. Cell. Biol 16, 1115–1125 (1996).
Pulyaeva, H. et al. MT1-MMP correlates with MMP-2 activation potential seen after epithelial to mesenchymal transition in human breast carcinoma cells. Clin. Exp. Metastasis 15, 111–120 (1997).
Sternlicht, M. D. et al. The stromal proteinase MMP3/stromelysin-1 promotes mammary carcinogenesis. Cell 98, 137–146 (1999).
Yoshioka, K., Nakamori, S. & Itoh, K. Overexpression of small GTP-binding protein RhoA promotes invasion of tumor cells. Cancer Res. 59, 2004–2010 (1999).
Condeelis, J., Jones, J. & Segall, J. E. Chemotaxis of metastatic tumor cells: clues to mechanisms from the Dictyostelium paradigm. Cancer Metastasis Rev. 11, 55–68 (1992).
Yumura, S., Mori, H. & Fukui, Y. Localization of actin and myosin for the study of ameboid movement in Dictyostelium using improved immunofluorescence. J. Cell Biol. 99, 894–899 (1984).
Devreotes, P. N. & Zigmond, S. H. Chemotaxis in eukaryotic cells: a focus on leukocytes and Dictyostelium. Annu. Rev. Cell Biol. 4, 649–686 (1988).
Fey, P., Stephens, S., Titus, M. A. & Chisholm, R. L. SadA, a novel adhesion receptor in Dictyostelium. J. Cell Biol. 159, 1109–1119 (2002).
Farina, K. L. et al. Cell motility of tumor cells visualized in living intact primary tumors using green fluorescent protein. Cancer Res. 58, 2528–2532 (1998). Fascinating in vivo imaging of amoeboid tumour-cell movement.
Friedl, P., Borgmann, S. & Brocker, E. B. Leukocyte crawling through extracellular matrix and the Dictyostelium paradigm of movement: lessons from a social amoeba. J. Leukoc. Biol. 70, 491–509 (2001).
Lewis, W. H. On the locomotion of the polymorphonuclear neutrophiles of the rat in autoplasma cultures. Bull. Johns Hopkins. Hosp. 4, 273–279 (1934). One of the first papers showing shape change as a mechanism to bypass ECM barriers.
Werr, J., Xie, X., Hedqvist, P., Ruoslahti, E. & Lindbom, L. Beta1 integrins are critically involved in neutrophil locomotion in extravascular tissue in vivo. J. Exp. Med. 187, 2091–2096 (1998).
Brakebusch, C. et al. Beta1 integrin is not essential for hematopoiesis but is necessary for the T cell-dependent IgM antibody response. Immunity 16, 465–477 (2002).
Haston, W. S., Shields, J. M. & Wilkinson, P. C. Lymphocyte locomotion and attachment on two-dimensional surfaces and in three-dimensional matrices. J. Cell Biol. 92, 747–752 (1982). Provides the first example of ‘non-adhesive’ migration in 3D collagen lattices.
Mandeville, J. T., Lawson, M. A. & Maxfield, F. R. Dynamic imaging of neutrophil migration in three dimensions: mechanical interactions between cells and matrix. J. Leukoc. Biol. 61, 188–200 (1997).
Verschueren, H., de Baetselier, P. & Bereiter-Hahn, J. Dynamic morphology of metastatic mouse T-lymphoma cells invading through monolayers of 10T1/2 cells. Cell Motil. Cytoskeleton 20, 203–214 (1991).
Rintoul, R. C. & Sethi, T. The role of extracellular matrix in small-cell lung cancer. Lancet Oncol. 2, 437–442 (2002).
Falcioni, R. et al. Expression of beta 1, beta 3, beta 4, and beta 5 integrins by human lung carcinoma cells of different histotypes. Exp. Cell Res. 210, 113–122 (1994).
Jaspars, L. H., Bonnet, P., Bloemena, E. & Meijer, C. J. Extracellular matrix and beta 1 integrin expression in nodal and extranodal T-cell lymphomas. J. Pathol. 178, 36–43 (1996).
Kraus, A. C. et al. In vitro chemo- and radio-resistance in small cell lung cancer correlates with cell adhesion and constitutive activation of AKT and MAP kinase pathways. Oncogene 21, 8683–8695 (2002).
Jacques, T. S. et al. Neural precursor cell chain migration and division are regulated through different beta1 integrins. Development 125, 3167–3177 (1998).
El Fahime, E., Torrente, Y., Caron, N. J., Bresolin, M. D. & Tremblay, J. P. In vivo migration of transplanted myoblasts requires matrix metalloproteinase activity. Exp. Cell Res. 258, 279–287 (2000).
Page, D. L., Anderson, T. J. & Sakamoto, G. in Diagnostic Histopathology of the Breast 219–222 (Churchill Livingstone, New York, 1987).
Pitts, W. C. et al. Carcinomas with metaplasia and sarcomas of the breast. Am. J. Clin. Pathol. 95, 623–632 (1991).
Sood, A. K. et al. Molecular determinants of ovarian cancer plasticity. Am. J. Pathol. 158, 1279–1288 (2001).
Seftor, E. A. et al. Molecular determinants of human uveal melanoma invasion and metastasis. Clin. Exp. Metastasis 19, 233–246 (2002).
Davidson, L. A. & Keller, R. E. Neural tube closure in Xenopus laevis involves medial migration, directed protrusive activity, cell intercalation and convergent extension. Development 126, 4547–4556 (1999).
Klinowska, T. C. et al. Laminin and beta1 integrins are crucial for normal mammary gland development in the mouse. Dev. Biol. 215, 13–32 (1999).
Simian, M. et al. The interplay of matrix metalloproteinases, morphogens and growth factors is necessary for branching of mammary epithelial cells. Development 128, 3117–3131 (2001).
Hiraoka, N., Allen, E., Apel, I. J., Gyetko, M. R. & Weiss, S. J. Matrix metalloproteinases regulate neovascularization by acting as pericellular fibrinolysins. Cell 95, 365–377 (1998).
Collen, A. et al. Membrane-type matrix metalloproteinase-mediated angiogenesis in a fibrin-collagen matrix. Blood 101, 1810–1817 (2003).
Vaughan, R. B. & Trinkaus, J. P. Movements of epithelial cell sheets in vitro. J. Cell Sci. 1, 407–413 (1966).
Kolega, J. The movement of cell clusters in vitro: morphology and directionality. J. Cell Sci. 49, 15–32 (1981). Provides a detailed description of how clustered cells move as a functional unit.
Friedl, P. et al. Migration of coordinated cell clusters in mesenchymal and epithelial cancer explants in vitro. Cancer Res. 55, 4557–4560 (1995).
Nabeshima, K. et al. Ultrastructural study of TPA-induced cell motility: human well-differentiated rectal adenocarcinoma cells move as coherent sheets via localized modulation of cell–cell adhesion. Clin. Exp. Metastasis 13, 499–508 (1995).
Hegerfeldt, Y., Tusch, M., Brocker, E. B. & Friedl, P. Collective cell movement in primary melanoma explants: plasticity of cell-cell interaction, β1-integrin function, and migration strategies. Cancer Res. 62, 2125–2130 (2002). First example of collective–amoeboid transition after blocking of β1-integrins — another escape mechanism.
Nabeshima, K. et al. Front-cell-specific expression of membrane-type 1 matrix metalloproteinase and gelatinase A during cohort migration of colon carcinoma cells induced by hepatocyte growth factor/scatter factor. Cancer Res. 60, 3364–3369 (2000).
Bell, C. D. & Waizbard, E. Variability of cell size in primary and metastatic human breast carcinoma. Invasion Metastasis 6, 11–20 (1986).
Nabeshima, K., Inoue, T., Shimao, Y., Kataoka, H. & Koono, M. Cohort migration of carcinoma cells: differentiated colorectal carcinoma cells move as coherent cell clusters or sheets. Histol. Histopathol. 14, 1183–1197 (1999).
Ackerman, A. B. & Ragaz, A. in The Lives of Lesions (ed. Ackerman, A. B.) 147–158 (Masson Publishers, New York, 1984).
Hashizume, R., Koizumi, H., Ihara, A., Ohta, T. & Uchikoshi, T. Expression of beta-catenin in normal breast tissue and breast carcinoma: a comparative study with epithelial cadherin and alpha-catenin. Histopathology 29, 139–146 (1996).
Madhavan, M. et al. Cadherins as predictive markers of nodal metastasis in breast cancer. Mod. Pathol. 14, 423–427 (2001).
Byers, S. W., Sommers, C. L., Hoxter, B., Mercurio, A. M. & Tozeren, A. Role of E-cadherin in the response of tumor cell aggregates to lymphatic, venous and arterial flow: measurement of cell–cell adhesion strength. J. Cell Sci. 108, 2053–2064 (1995).
Brandt, B. et al. Isolation of prostate-derived single cells and cell clusters from human peripheral blood. Cancer Res. 56, 4556–4561 (1996).
Pishvaian, M. J. et al. Cadherin-11 is expressed in invasive breast cancer cell lines. Cancer Res. 59, 947–952 (1999).
Hsu, M., Andl, T., Li, G., Meinkoth, J. L. & Herlyn, M. Cadherin repertoire determines partner-specific gap junctional communication during melanoma progression. J. Cell Sci. 113, 1535–1542 (2000).
Moll, R., Mitze, M., Frixen, U. H. & Birchmeier, W. Differential loss of E-cadherin expression in infiltrating ductal and lobular breast carcinomas. Am. J. Pathol. 143, 1731–1742 (1993).
Klein, C. E., Steinmayer, T., Kaufmann, D., Weber, L. & Brocker, E. B. Identification of a melanoma progression antigen as integrin VLA-2. J. Invest. Dermatol. 96, 281–284 (1991).
Trikha, M. et al. The high affinity alphaIIb beta3 integrin is involved in invasion of human melanoma cells. Cancer Res. 57, 2522–2528 (1997).
Strobel, T. & Cannistra, S. A. Beta1-integrins partly mediate binding of ovarian cancer cells to peritoneal mesothelium in vitro. Gynecol. Oncol. 73, 362–367 (1999).
Chao, C., Lotz, M. M., Clarke, A. C. & Mercurio, A. M. A function for the integrin alpha6beta4 in the invasive properties of colorectal carcinoma cells. Cancer Res. 56, 4811–4819 (1996).
Cress, A. E., Rabinovitz, I., Zhu, W. & Nagle, R. B. The alpha 6 beta 1 and alpha 6 beta 4 integrins in human prostate cancer progression. Cancer Metastasis Rev. 14, 219–228 (1995).
Danen, E. H. J. et al. Regulation of integrin-mediated adhesion to laminin and collagen in human melanocytes and in non-metastatic and highly metastatic human melanoma cells. Int. J. Cancer 54, 315–321 (1993).
Zutter, M. M., Santoro, S. A., Staatz, W. D. & Tsung, Y. L. Re-expression of the alpha 2 beta 1 integrin abrogates the malignant phenotype of breast carcinoma cells. Proc. Natl Acad. Sci. USA 92, 7411–7415 (1995).
Schirner, M. et al. Integrin alpha5beta1: a potent inhibitor of experimental lung metastasis. Clin. Exp. Metastasis 16, 427–435 (1998).
Mignatti, P., Robbins, E. & Rifkin, D. B. Tumor invasion through the human amniotic membrane: requirement for a proteinase cascade. Cell 47, 487–498 (1986).
Kurschat, P. et al. Tissue inhibitor of matrix metalloproteinase-2 regulates matrix metalloproteinase-2 activation by modulation of membrane-type 1 matrix metalloproteinase activity in high and low invasive melanoma cell lines. J. Biol. Chem. 274, 21056–21062 (1999).
Ntayi, C., Lorimier, S., Berthier-Vergnes, O., Hornebeck, W. & Bernard, P. Cumulative influence of matrix metalloproteinase-1 and -2 in the migration of melanoma cells within three-dimensional type I collagen lattices. Exp. Cell Res. 270, 110–118 (2001).
Hotary, K., Allen, E., Punturieri, A., Yana, I. & Weiss, S. J. Regulation of cell invasion and morphogenesis in a three-dimensional type I collagen matrix by membrane-type matrix metalloproteinases 1, 2, and 3. J. Cell Biol. 149, 1309–1323 (2000). Together with references 63 and 159, this paper shows that MT1-MMP is the most important collagenase in invading tumour cells. They formally prove the concept that pericellular proteolysis contributes to invasion.
Wang, X., Fu, X., Brown, P. D., Crimmin, M. J. & Hoffman, R. M. Matrix metalloproteinase inhibitor BB-94 (batimastat) inhibits human colon tumor growth and spread in a patient-like orthotopic model in nude mice. Cancer Res. 54, 4726–4728 (1994).
Maki, H. et al. Augmented anti-metastatic efficacy of a selective matrix metalloproteinase inhibitor, MMI-166, in combination with CPT-11. Clin. Exp. Metastasis 19, 519–526 (2002).
Kruger, A. et al. Hydroxamate-type matrix metalloproteinase inhibitor batimastat promotes liver metastasis. Cancer Res. 61, 1272–1275 (2001).
Della, P. P. et al. Combined treatment with serine protease inhibitor aprotinin and matrix metalloproteinase inhibitor Batimastat (BB-94) does not prevent invasion of human esophageal and ovarian carcinoma cells in vivo. Anticancer Res. 19, 3809–3816 (1999).
Zucker, S., Cao, J. & Chen, W. T. Critical appraisal of the use of matrix metalloproteinase inhibitors in cancer treatment. Oncogene 19, 6642–6650 (2000).
Coussens, L. M., Fingleton, B. & Matrisian, L. M. Matrix metalloproteinase inhibitors and cancer: trials and tribulations. Science 295, 2387–2392 (2002).
Overall, C. M. & Lopez-Otin, C. Strategies for MMP inhibition in cancer: innovations for the post-trial era. Nature Rev. Cancer 2, 657–672 (2002). References 127–129 summarize and explain the failure of clinical trials of matrix metalloproteinase inhibitors in late-stage cancer patients. It sets the scene for future work in the MMP field.
Lochter, A., Navre, M., Werb, Z. & Bissell, M. J. alpha1 and alpha2 integrins mediate invasive activity of mouse mammary carcinoma cells through regulation of stromelysin-1 expression. Mol. Biol. Cell 10, 271–282 (1999).
Sternlicht, M. D. & Werb, Z. How matrix metalloproteinases regulate cell behavior. Annu. Rev. Cell Dev. Biol. 17, 463–516 (2001).
Sakkab, D. et al. Signaling of hepatocyte growth factor/scatter factor (HGF) to the small GTPase Rap1 via the large docking protein Gab1 and the adapter protein CRKL. J. Biol. Chem. 275, 10772–10778 (2000).
Quirt, I. et al. Phase II study of marimastat (BB-2516) in malignant melanoma: a clinical and tumor biopsy study of the National Cancer Institute of Canada Clinical Trials Group. Invest. New Drugs 20, 431–437 (2002).
Bonomi, P. Matrix metalloproteinases and matrix metalloproteinase inhibitors in lung cancer. Semin. Oncol. 29, 78–86 (2002).
Harbeck, N., Kates, R. E. & Schmitt, M. Clinical relevance of invasion factors urokinase-type plasminogen activator and plasminogen activator inhibitor type 1 for individualized therapy decisions in primary breast cancer is greatest when used in combination. J. Clin. Oncol. 20, 1000–1007 (2002).
Leung-Toung, R., Li, W., Tam, T. F. & Karimian, K. Thiol-dependent enzymes and their inhibitors: a review. Curr. Med. Chem. 9, 979–1002 (2002).
Fassler, R. & Meyer, M. Consequences of lack of beta 1 integrin gene expression in mice. Genes Dev. 9, 1896–1908 (1995).
Fassler, R. et al. Lack of beta 1 integrin gene in embryonic stem cells affects morphology, adhesion, and migration but not integration into the inner cell mass of blastocysts. J. Cell Biol. 128, 979–988 (1995). Together with references 35, 76 and 77, this paper shows that β1 integrins can be dispensable for cell movement and positioning in 3D tissue structures.
Lombardi, L. et al. Ultrastructural cytoskeleton alterations and modification of actin expression in the NIH/3T3 cell line after transformation with Ha-ras-activated oncogene. Cell Motil. Cytoskeleton 15, 220–229 (1990).
Dartsch, P. C., Ritter, M., Haussinger, D. & Lang, F. Cytoskeletal reorganization in NIH 3T3 fibroblasts expressing the Ras oncogene. Eur. J. Cell Biol. 63, 316–325 (1994).
Khosravi-Far, R. et al. Dbl and Vav mediate transformation via mitogen-activated protein kinase pathways that are distinct from those activated by oncogenic Ras. Mol. Cell. Biol. 14, 6848–6857 (1994).
Qiu, R. G., Chen, J., McCormick, F. & Symons, M. A role for Rho in Ras transformation. Proc. Natl Acad. Sci. USA 92, 11781–11785 (1995).
Whittard, J. D. & Akiyama, S. K. Activation of beta1 integrins induces cell–cell adhesion. Exp. Cell Res. 263, 65–76 (2001).
Robinson, E. E., Zazzali, K. M., Corbett, S. A. & Foty, R. A. Alpha5beta1 integrin mediates strong tissue cohesion. J. Cell Sci. 116, 377–386 (2003).
Whittard, J. D. et al. E-cadherin is a ligand for integrin alpha2beta1. Matrix Biol. 21, 525–532 (2002).
Hynes, R. O. & Zhao, Q. The evolution of cell adhesion. J. Cell Biol. 150, F89–F96 (2000). Insightful overview of how adhesion receptors evolved in the context of increasing tissue complexity and segregation.
Blanchoin, L. et al. Direct observation of dendritic actin filament networks nucleated by Arp2/3 complex and WASP/Scar proteins. Nature 404, 1007–1011 (2000).
Nobes, C. D. & Hall, A. Rho, Rac, and Cdc42 GTPases regulate the assembly of multimolecular focal complexes associated with actin stress fibers, lamellipodia, and filopodia. Cell 81, 53–62 (1995).
Ren, X. D. et al. Physical association of the small GTPase Rho with a 68-kDa phosphatidylinositol 4-phosphate 5-kinase in Swiss 3T3 cells. Mol. Biol. Cell 7, 435–442 (1996).
Leopoldt, D. et al. Gbetagamma stimulates phosphoinositide 3-kinase-gamma by direct interaction with two domains of the catalytic p110 subunit. J. Biol. Chem. 273, 7024–7029 (1998).
Tsutsumi, S., Gupta, S. K., Hogan, V., Collard, J. G. & Raz, A. Activation of small GTPase Rho is required for autocrine motility factor signaling. Cancer Res. 62, 4484–4490 (2002).
Miyamoto, S. et al. Integrin function: molecular hierarchies of cytoskeletal and signaling molecules. J. Cell Biol. 131, 791–805 (1995).
Calderwood, D. A., Shattil, S. J. & Ginsberg, M. H. Integrins and actin filaments: reciprocal regulation of cell adhesion and signaling. J. Biol. Chem. 275, 22607–22610 (2000).
Degani, S. et al. The integrin cytoplasmic domain-associated protein ICAP-1 binds and regulates Rho family GTPases during cell spreading. J. Cell Biol. 156, 377–387 (2002).
DeMali, K. A., Barlow, C. A. & Burridge, K. Recruitment of the Arp2/3 complex to vinculin: coupling membrane protrusion to matrix adhesion. J. Cell Biol. 159, 881–891 (2002).
Schwartz, M. A. & Shattil, S. J. Signaling networks linking integrins and Rho family GTPases. Trends Biochem. Sci. 25, 388–391 (2000).
Ilic, D. et al. Reduced cell motility and anhanced focal adhesion contact formation in cells from FAK-deficient mice. Nature 377, 539–544 (1995).
Mueller, S. C. et al. A novel protease-docking function of integrin at invadopodia. J. Biol. Chem. 274, 24947–24952 (1999).
Ohuchi, E. et al. Membrane type 1 matrix metalloproteinase digests interstitial collagens and other extracellular matrix macromolecules. J. Biol. Chem. 272, 2446–2451 (1997).
Dumin, J. A. et al. Pro-collagenase-1 (matrix metalloproteinase-1) binds the alpha(2)beta(1) integrin upon release from keratinocytes migrating on type I collagen. J. Biol. Chem. 276, 29368–29374 (2001).
Brooks, P. C., Silletti, S., von Schalscha, T. L., Friedlander, M. & Cheresh, D. A. Disruption of angiogenesis by PEX, a noncatalytic metalloproteinase fragment with integrin binding activity. Cell 92, 391–400 (1998).
Ellerbroek, S. M., Wu, Y. I., Overall, C. M. & Stack, M. S. Functional interplay between type I collagen and cell surface matrix metalloproteinase activity. J. Biol. Chem. 276, 24833–24842 (2001).
Galvez, B. G., Matias-Roman, S., Yanez-Mo, M., Sanchez-Madrid, F. & Arroyo, A. G. ECM regulates MT1-MMP localization with beta1 or alphavbeta3 integrins at distinct cell compartments modulating its internalization and activity on human endothelial cells. J. Cell Biol. 159, 509–521 (2002).
Tam, E. M., Wu, Y. I., Butler, G. S., Stack, M. S. & Overall, C. M. Collagen binding properties of the membrane type-1 matrix metalloproteinase (MT1-MMP) hemopexin C domain. The ectodomain of the 44-kDa autocatalytic product of MT1-MMP inhibits cell invasion by disrupting native type I collagen cleavage. J. Biol. Chem. 277, 39005–39014 (2002).
Fukata, Y., Amano, M. & Kaibuchi, K. Rho-Rho-kinase pathway in smooth muscle contraction and cytoskeletal reorganization of non-muscle cells. Trends Pharmacol. Sci. 22, 32–39 (2001).
Wear, M. A., Schafer, D. A. & Cooper, J. A. Actin dynamics: assembly and disassembly of actin networks. Curr. Biol. 10, R891–R895 (2000).
Zeng, L. et al. PTP alpha regulates integrin-stimulated FAK autophosphorylation and cytoskeletal rearrangement in cell spreading and migration. J. Cell Biol. 160, 137–146 (2003).
Pfaff, M., Du, X. & Ginsberg, M. H. Calpain cleavage of integrin beta cytoplasmic domains. FEBS Lett. 460, 17–22 (1999).
Moss, M. L. & Lambert, M. H. Shedding of membrane proteins by ADAM family proteases. Essays Biochem. 38, 141–153 (2002).
Carragher, N. O., Levkau, B., Ross, R. & Raines, E. W. Degraded collagen fragments promote rapid disassembly of smooth muscle focal adhesions that correlates with cleavage of pp125(FAK), paxillin, and talin. J. Cell Biol. 147, 619–630 (1999).
Bretscher, M. S. Getting membrane flow and the cytoskeleton to cooperate in moving cells. Cell 87, 601–606 (1996).
Firtel, R. A. & Meili, R. Dictyostelium: a model for regulated cell movement during morphogenesis. Curr. Opin. Genet. Dev. 10, 421–427 (2000).
Scotton, C. J. et al. Multiple actions of the chemokine CXCL12 on epithelial tumor cells in human ovarian cancer. Cancer Res. 62, 5930–5938 (2002).
Price, J. T., Tiganis, T., Agarwal, A., Djakiew, D. & Thompson, E. W. Epidermal growth factor promotes MDA-MB-231 breast cancer cell migration through a phosphatidylinositol 3′-kinase and phospholipase C-dependent mechanism. Cancer Res. 59, 5475–5478 (1999).
Sawada, K. et al. Alendronate inhibits lysophosphatidic acid-induced migration of human ovarian cancer cells by attenuating the activation of Rho. Cancer Res. 62, 6015–6020 (2002).
Doerr, M. E. & Jones, J. I. The roles of integrins and extracellular matrix proteins in the insulin-like growth factor 1-stimulated chemotaxis of human breast cancer cells. J. Biol. Chem. 271, 2443–2447 (1996).
Tumour-cell invasion and migration: diversity and escape mechanisms
Chambers, A. F., Groom, A. C. & MacDonald, I. C. Dissemination and growth of cancer cells in metastatic sites. Nature Rev. Cancer 2, 563–572 (2002).
Friedl, P. & Bröcker, E. -B. The biology of cell locomotion within three-dimensional extracellular matrix. Cell. Mol. Life Sci. 57, 41–64 (2000).
Abercrombie, M., Dunn, G. A. & Heath, J. P. The shape and movement of fibroblasts in culture. Soc. Gen. Physiol. Ser. 32, 57–70 (1977).
Lauffenburger, D. A. & Horwitz, A. F. Cell migration: a physically integrated molecular process. Cell 84, 359–369 (1996). The ‘bible’ for cell migration researchers.
Adams, J. C. Cell-matrix contact structures. Cell. Mol. Life Sci. 58, 371–392 (2001).
Burridge, K. & Chrzanowska-Wodicka, M. Focal adhesions, contractility, and signaling. Annu. Rev. Cell Dev. Biol. 12, 463–519 (1996).
Cramer, L. P. Organization and polarity of actin filament networks in cells: implications for the mechanism of myosin-based cell motility. Biochem. Soc. Symp. 65, 173–205 (1999).
Rohatgi, R. et al. The interaction between N-WASP and the Arp2/3 complex links Cdc42-dependent signals to actin assembly. Cell 97, 221–231 (1999).
Hynes, R. O. Integrins: bidirectional, allosteric signaling machines. Cell 110, 673–687 (2002).
Otey, C. A. & Burridge, K. Patterning of the membrane cytoskeleton by the extracellular matrix. Semin. Cell Biol. 1, 391–399 (1990).
Zamir, E. et al. Dynamics and segregation of cell-matrix adhesions in cultured fibroblasts. Nature Cell Biol. 2, 191–196 (2000).
Zamir, E. & Geiger, B. Molecular complexity and dynamics of cell-matrix adhesions. J. Cell Sci. 114, 3583–3590 (2001). References 11 and 12 explain the dynamic nature and diversity of cell-matrix interactions. They provide the molecular basis for plasticity and adaptation responses in cell migration.
Regen, C. M. & Horwitz, A. F. Dynamics of beta 1 integrin-mediated adhesive contacts in motile fibroblasts. J. Cell Biol. 119, 1347–1359 (1992).
Smilenov, L. B., Mikhailov, A., Pelham, R. J., Marcantonio, E. E. & Gundersen, G. G. Focal adhesion motility revealed in stationary fibroblasts. Science 286, 1172–1174 (1999).
Cukierman, E., Pankov, R., Stevens, D. R. & Yamada, K. M. Taking cell-matrix adhesions to the third dimension. Science 294, 1708–1712 (2001).
Rabinovitz, I. & Mercurio, A. M. The integrin alpha6beta4 functions in carcinoma cell migration on laminin-1 by mediating the formation and stabilization of actin-containing motility structures. J. Cell Biol. 139, 1873–1884 (1997).
Leavesley, D. I., Ferguson, G. D., Wayner, E. A. & Cheresh, D. A. Requirement of the integrin beta 3 subunit for carcinoma cell spreading or migration on vitronectin and fibrinogen. J. Cell Biol. 117, 1101–1107 (1992).
Maaser, K. et al. Functional hierarchy of simultaneously expressed adhesion receptors: integrin alpha2beta1 but not CD44 mediates MV3 melanoma cell migration and matrix reorganization within three-dimensional hyaluronan-containing collagen matrices. Mol. Biol. Cell 10, 3067–3079 (1999).
Friedl, P. et al. Migration of highly aggressive MV3 melanoma cells in 3-dimensional collagen lattices results in local matrix reorganization and shedding of alpha2 and beta1 integrins and CD44. Cancer Res. 57, 2061–2070 (1997).
Friedl, P. & Wolf, K. Proteolytic and non–proteolytic migration in tumor cells and leukocytes. Biochem. Soc. Symp. (in the press).
Byers, H. R. & Fujiwara, K. Stress fibers in cells in situ: immunofluorescence visualization with antiactin, antimyosin, and anti-alpha-actinin. J. Cell Biol. 93, 804–811 (1982).
Katoh, K. et al. Rho-kinase-mediated contraction of isolated stress fibers. J. Cell Biol. 153, 569–584 (2001).
Chew, T. L., Wolf, W. A., Gallagher, P. J., Matsumura, F. & Chisholm, R. L. A fluorescent resonant energy transfer-based biosensor reveals transient and regional myosin light chain kinase activation in lamella and cleavage furrows. J. Cell Biol. 156, 543–553 (2002).
Kaibuchi, K., Kuroda, S. & Amano, M. Regulation of the cytoskeleton and cell adhesion by the Rho family GTPases in mammalian cells. Annu. Rev. Biochem. 68, 459–486 (1999).
Totsukawa, G. et al. Distinct roles of ROCK (Rho-kinase) and MLCK in spatial regulation of MLC phosphorylation for assembly of stress fibers and focal adhesions in 3T3 fibroblasts. J. Cell Biol. 150, 797–806 (2000).
Kamm, K. E. & Stull, J. T. Dedicated myosin light chain kinases with diverse cellular functions. J. Biol. Chem. 276, 4527–4530 (2001).
Somlyo, A. V. et al. Rho kinase and matrix metalloproteinase inhibitors cooperate to inhibit angiogenesis and growth of human prostate cancer xenotransplants. FASEB J. 17, 223–234 (2003).
Verkhovsky, A. B., Svitkina, T. M. & Borisy, G. G. Myosin II filament assemblies in the active lamella of fibroblasts: their morphogenesis and role in the formation of actin filament bundles. J. Cell Biol. 131, 989–1002 (1995).
Friedl, P. & Brocker, E. B. in Image Analysis. Methods and Applications 2nd edn (ed. Hader, D. P.) 9–21 (CRC Press, London, 2001).
Palecek, S. P., Loftus, J. C., Ginsberg, M. H., Lauffenburger, D. A. & Horwitz, A. F. Integrin-ligand binding properties govern cell migration speed through cell-substratum adhesiveness. Nature 385, 537–540 (1997).
Ballestrem, C., Hinz, B., Imhof, B. A. & Wehrle-Haller, B. Marching at the front and dragging behind: differential alphaVbeta3-integrin turnover regulates focal adhesion behavior. J. Cell Biol. 155, 1319–1332 (2001).
Potter, D. A. et al. Calpain regulates actin remodeling during cell spreading. J. Cell Biol. 141, 647–662 (1998).
Friedl, P., Zanker, K. S. & Bröcker, E. -B. Cell migration strategies in 3-D extracellular matrix: differences in morphology, cell matrix interactions, and integrin function. Microsc. Res. Tech. 43, 369–378 (1998).
Entschladen, F., Niggemann, B., Zänker, K. S. & Friedl, P. Differential requirement of protein tyrosine kinases and protein kinase C in the regulation of T cell locomotion in three-dimensional collagen matrices. J. Immunol. 159, 3203–3210 (1997).
Friedl, P., Entschladen, F., Conrad, C., Niggemann, B. & Zanker, K. S. CD4+ T lymphocytes migrating in three-dimensional collagen lattices lack focal adhesions and utilize beta1 integrin-independent strategies for polarization, interaction with collagen fibers and locomotion. Eur. J. Immunol. 28, 2331–2343 (1998).
Yamada, K. M. et al. Monoclonal antibody and synthetic peptide inhibitors of human tumor cell migration. Cancer Res. 50, 4485–4496 (1990).
Filardo, E. J., Brooks, P. C., Deming, S. L., Damsky, C. & Cheresh, D. A. Requirement of the NPXY motif in the integrin beta 3 subunit cytoplasmic tail for melanoma cell migration in vitro and in vivo. J. Cell Biol. 130, 441–450 (1995).
Flanagan, L. A. et al. Filamin A, the Arp2/3 complex, and the morphology and function of cortical actin filaments in human melanoma cells. J. Cell Biol. 155, 511–517 (2001).
Sameni, M., Moin, K. & Sloane, B. F. Imaging proteolysis by living human breast cancer cells. Neoplasia 2, 496–504 (2001).
Rosenthal, E. L., Hotary, K., Bradford, C. & Weiss, S. J. Role of membrane type 1-matrix metalloproteinase and gelatinase A in head and neck squamous cell carcinoma invasion in vitro. Otolaryngol. Head Neck Surg. 121, 337–343 (1999).
Koblinski, J. E., Ahram, M. & Sloane, B. F. Unraveling the role of proteases in cancer. Clin. Chim. Acta 291, 113–135 (2000).
Hofmann, U. B., Westphal, J. R., van Muijen, G. N. & Ruiter, D. J. Matrix metalloproteinases in human melanoma. J. Invest. Dermatol. 115, 337–344 (2000).
Deryugina, E. I., Bourdon, M. A., Reisfeld, R. A. & Strongin, A. Remodeling of collagen matrix by human tumor cells requires activation and cell surface association of matrix metalloproteinase-2. Cancer Res. 58, 3743–3750 (1998).
Maekawa, K., Sato, H., Furukawa, M. & Yoshizaki, T. Inhibition of cervical lymph node metastasis by marimastat (BB-2516) in an orthotopic oral squamous cell carcinoma implantation model. Clin. Exp. Metastasis 19, 513–518 (2002).
Rudolph-Owen, L. A., Chan, R., Muller, W. J. & Matrisian, L. M. The matrix metalloproteinase matrilysin influences early-stage mammary tumorigenesis. Cancer Res. 58, 5500–5506 (1998).
Sahai, E., Olson, M. F. & Marshall, C. J. Cross-talk between Ras and Rho signalling pathways in transformation favours proliferation and increased motility. EMBO J. 20, 755–766 (2001).
Clark, E. A., Golub, T. R., Lander, E. S. & Hynes, R. O. Genomic analysis of metastasis reveals an essential role for RhoC. Nature 406, 532–535 (2000).
Itoh, K. et al. An essential part for Rho-associated kinase in the transcellular invasion of tumor cells. Nature Med. 5, 221–225 (1999).
Kaneko, K., Satoh, K., Masamune, A., Satoh, A. & Shimosegawa, T. Myosin light chain kinase inhibitors can block invasion and adhesion of human pancreatic cancer cell lines. Pancreas 24, 34–41 (2002).
Allman, R., Cowburn, P. & Mason, M. In vitro and in vivo effects of a cyclic peptide with affinity for the alpha(nu)beta3 integrin in human melanoma cells. Eur. J. Cancer 36, 410–422 (2000).
Gianelli, G., Falk-Marzillier, J., Schiraldi, O., Stetler-Stevenson, W. G. & Quaranta, V. Induction of cell migration by matrix metalloprotease-2 cleavage of laminin-5. Science 277, 225–228 (1997).
Alper, O. et al. Epidermal growth factor receptor signaling and the invasive phenotype of ovarian carcinoma cells. J. Natl Cancer Inst. 93, 1375–1384 (2001).
Seftor, R. E. et al. Cooperative interactions of laminin 5 gamma2 chain, matrix metalloproteinase-2, and membrane type-1-matrix/metalloproteinase are required for mimicry of embryonic vasculogenesis by aggressive melanoma. Cancer Res. 61, 6322–6327 (2001).
Brooks, P. C. et al. Insulin-like growth factor receptor cooperates with integrin alpha v beta 5 to promote tumor cell dissemination in vivo. J. Clin. Invest. 99, 1390–1398 (1997).
Thiery, J. P. Epithelial–mesenchymal transitions in tumour progression. Nature Rev. Cancer 2, 442–454 (2002). Comprehensive review on a classic example of plasticity during tumour invasion.
Enterline, H. T. & Cohen, D. R. The ameboid motility of human and animal neoplastic cells. Cancer 3, 1033–1038 (1950).
Wood, S. Jr. Pathogenesis of metastasis formation observed in vivo in the rabbit ear chamber. Arch. Pathol. 66, 550–568 (1958).
Wolf, K. et al. Compensation mechanism in tumor cell migration: mesenchymal–amoeboid transition after blocking of pericellular proteolysis. J. Cell Biol. 160, 267–277 (2003). A novel escape mechanism after the blocking of pericellular proteolysis. By converting to a more ‘primitive’ amoeboid migration mode, previously proteolytic tumour cells continue to move non-proteolytically by path-finding migration strategies.
Paulus, W., Baur, I., Beutler, A. S. & Reeves, S. A. Diffuse brain invasion of glioma cells requires beta 1 integrins. Lab. Invest. 75, 819–826 (1996).
Polette, M. et al. Association of fibroblastoid features with the invasive phenotype in human bronchial cancer cell lines. Clin. Exp. Metastasis 16, 105–112 (1998).
Tester, A. M., Ruangpani, N., Anderso, R. L. & Thompson, E. W. MMP-9 secretion and MMP-2 activation distinguish invasive and metastatic sublines of a mouse mammary carcinoma system showing epithelial–mesenchymal transition traits. Clin. Exp. Metastasis 18, 553–560 (2000).
Putz, E. et al. Phenotypic characteristics of cell lines derived from disseminated cancer cells in bone marrow of patients with solid epithelial tumors: establishment of working models for human micrometastases. Cancer Res. 59, 241–248 (1999).
d’Ortho, M. P. et al. MT1-MMP on the cell surface causes focal degradation of gelatin films. FEBS Lett. 421, 159–164 (1998).
Jeffers, M., Rong, S. & Vande, W. G. Enhanced tumorigenicity and invasion-metastasis by hepatocyte growth factor/scatter factor-Met signalling in human cells concomitant with induction of the urokinase proteolysis network. Mol. Cell. Biol 16, 1115–1125 (1996).
Pulyaeva, H. et al. MT1-MMP correlates with MMP-2 activation potential seen after epithelial to mesenchymal transition in human breast carcinoma cells. Clin. Exp. Metastasis 15, 111–120 (1997).
Sternlicht, M. D. et al. The stromal proteinase MMP3/stromelysin-1 promotes mammary carcinogenesis. Cell 98, 137–146 (1999).
Yoshioka, K., Nakamori, S. & Itoh, K. Overexpression of small GTP-binding protein RhoA promotes invasion of tumor cells. Cancer Res. 59, 2004–2010 (1999).
Condeelis, J., Jones, J. & Segall, J. E. Chemotaxis of metastatic tumor cells: clues to mechanisms from the Dictyostelium paradigm. Cancer Metastasis Rev. 11, 55–68 (1992).
Yumura, S., Mori, H. & Fukui, Y. Localization of actin and myosin for the study of ameboid movement in Dictyostelium using improved immunofluorescence. J. Cell Biol. 99, 894–899 (1984).
Devreotes, P. N. & Zigmond, S. H. Chemotaxis in eukaryotic cells: a focus on leukocytes and Dictyostelium. Annu. Rev. Cell Biol. 4, 649–686 (1988).
Fey, P., Stephens, S., Titus, M. A. & Chisholm, R. L. SadA, a novel adhesion receptor in Dictyostelium. J. Cell Biol. 159, 1109–1119 (2002).
Farina, K. L. et al. Cell motility of tumor cells visualized in living intact primary tumors using green fluorescent protein. Cancer Res. 58, 2528–2532 (1998). Fascinating in vivo imaging of amoeboid tumour-cell movement.
Friedl, P., Borgmann, S. & Brocker, E. B. Leukocyte crawling through extracellular matrix and the Dictyostelium paradigm of movement: lessons from a social amoeba. J. Leukoc. Biol. 70, 491–509 (2001).
Lewis, W. H. On the locomotion of the polymorphonuclear neutrophiles of the rat in autoplasma cultures. Bull. Johns Hopkins. Hosp. 4, 273–279 (1934). One of the first papers showing shape change as a mechanism to bypass ECM barriers.
Werr, J., Xie, X., Hedqvist, P., Ruoslahti, E. & Lindbom, L. Beta1 integrins are critically involved in neutrophil locomotion in extravascular tissue in vivo. J. Exp. Med. 187, 2091–2096 (1998).
Brakebusch, C. et al. Beta1 integrin is not essential for hematopoiesis but is necessary for the T cell-dependent IgM antibody response. Immunity 16, 465–477 (2002).
Haston, W. S., Shields, J. M. & Wilkinson, P. C. Lymphocyte locomotion and attachment on two-dimensional surfaces and in three-dimensional matrices. J. Cell Biol. 92, 747–752 (1982). Provides the first example of ‘non-adhesive’ migration in 3D collagen lattices.
Mandeville, J. T., Lawson, M. A. & Maxfield, F. R. Dynamic imaging of neutrophil migration in three dimensions: mechanical interactions between cells and matrix. J. Leukoc. Biol. 61, 188–200 (1997).
Verschueren, H., de Baetselier, P. & Bereiter-Hahn, J. Dynamic morphology of metastatic mouse T-lymphoma cells invading through monolayers of 10T1/2 cells. Cell Motil. Cytoskeleton 20, 203–214 (1991).
Rintoul, R. C. & Sethi, T. The role of extracellular matrix in small-cell lung cancer. Lancet Oncol. 2, 437–442 (2002).
Falcioni, R. et al. Expression of beta 1, beta 3, beta 4, and beta 5 integrins by human lung carcinoma cells of different histotypes. Exp. Cell Res. 210, 113–122 (1994).
Jaspars, L. H., Bonnet, P., Bloemena, E. & Meijer, C. J. Extracellular matrix and beta 1 integrin expression in nodal and extranodal T-cell lymphomas. J. Pathol. 178, 36–43 (1996).
Kraus, A. C. et al. In vitro chemo- and radio-resistance in small cell lung cancer correlates with cell adhesion and constitutive activation of AKT and MAP kinase pathways. Oncogene 21, 8683–8695 (2002).
Jacques, T. S. et al. Neural precursor cell chain migration and division are regulated through different beta1 integrins. Development 125, 3167–3177 (1998).
El Fahime, E., Torrente, Y., Caron, N. J., Bresolin, M. D. & Tremblay, J. P. In vivo migration of transplanted myoblasts requires matrix metalloproteinase activity. Exp. Cell Res. 258, 279–287 (2000).
Page, D. L., Anderson, T. J. & Sakamoto, G. in Diagnostic Histopathology of the Breast 219–222 (Churchill Livingstone, New York, 1987).
Pitts, W. C. et al. Carcinomas with metaplasia and sarcomas of the breast. Am. J. Clin. Pathol. 95, 623–632 (1991).
Sood, A. K. et al. Molecular determinants of ovarian cancer plasticity. Am. J. Pathol. 158, 1279–1288 (2001).
Seftor, E. A. et al. Molecular determinants of human uveal melanoma invasion and metastasis. Clin. Exp. Metastasis 19, 233–246 (2002).
Davidson, L. A. & Keller, R. E. Neural tube closure in Xenopus laevis involves medial migration, directed protrusive activity, cell intercalation and convergent extension. Development 126, 4547–4556 (1999).
Klinowska, T. C. et al. Laminin and beta1 integrins are crucial for normal mammary gland development in the mouse. Dev. Biol. 215, 13–32 (1999).
Simian, M. et al. The interplay of matrix metalloproteinases, morphogens and growth factors is necessary for branching of mammary epithelial cells. Development 128, 3117–3131 (2001).
Hiraoka, N., Allen, E., Apel, I. J., Gyetko, M. R. & Weiss, S. J. Matrix metalloproteinases regulate neovascularization by acting as pericellular fibrinolysins. Cell 95, 365–377 (1998).
Collen, A. et al. Membrane-type matrix metalloproteinase-mediated angiogenesis in a fibrin-collagen matrix. Blood 101, 1810–1817 (2003).
Vaughan, R. B. & Trinkaus, J. P. Movements of epithelial cell sheets in vitro. J. Cell Sci. 1, 407–413 (1966).
Kolega, J. The movement of cell clusters in vitro: morphology and directionality. J. Cell Sci. 49, 15–32 (1981). Provides a detailed description of how clustered cells move as a functional unit.
Friedl, P. et al. Migration of coordinated cell clusters in mesenchymal and epithelial cancer explants in vitro. Cancer Res. 55, 4557–4560 (1995).
Nabeshima, K. et al. Ultrastructural study of TPA-induced cell motility: human well-differentiated rectal adenocarcinoma cells move as coherent sheets via localized modulation of cell–cell adhesion. Clin. Exp. Metastasis 13, 499–508 (1995).
Hegerfeldt, Y., Tusch, M., Brocker, E. B. & Friedl, P. Collective cell movement in primary melanoma explants: plasticity of cell-cell interaction, β1-integrin function, and migration strategies. Cancer Res. 62, 2125–2130 (2002). First example of collective–amoeboid transition after blocking of β1-integrins — another escape mechanism.
Nabeshima, K. et al. Front-cell-specific expression of membrane-type 1 matrix metalloproteinase and gelatinase A during cohort migration of colon carcinoma cells induced by hepatocyte growth factor/scatter factor. Cancer Res. 60, 3364–3369 (2000).
Bell, C. D. & Waizbard, E. Variability of cell size in primary and metastatic human breast carcinoma. Invasion Metastasis 6, 11–20 (1986).
Nabeshima, K., Inoue, T., Shimao, Y., Kataoka, H. & Koono, M. Cohort migration of carcinoma cells: differentiated colorectal carcinoma cells move as coherent cell clusters or sheets. Histol. Histopathol. 14, 1183–1197 (1999).
Ackerman, A. B. & Ragaz, A. in The Lives of Lesions (ed. Ackerman, A. B.) 147–158 (Masson Publishers, New York, 1984).
Hashizume, R., Koizumi, H., Ihara, A., Ohta, T. & Uchikoshi, T. Expression of beta-catenin in normal breast tissue and breast carcinoma: a comparative study with epithelial cadherin and alpha-catenin. Histopathology 29, 139–146 (1996).
Madhavan, M. et al. Cadherins as predictive markers of nodal metastasis in breast cancer. Mod. Pathol. 14, 423–427 (2001).
Byers, S. W., Sommers, C. L., Hoxter, B., Mercurio, A. M. & Tozeren, A. Role of E-cadherin in the response of tumor cell aggregates to lymphatic, venous and arterial flow: measurement of cell–cell adhesion strength. J. Cell Sci. 108, 2053–2064 (1995).
Brandt, B. et al. Isolation of prostate-derived single cells and cell clusters from human peripheral blood. Cancer Res. 56, 4556–4561 (1996).
Pishvaian, M. J. et al. Cadherin-11 is expressed in invasive breast cancer cell lines. Cancer Res. 59, 947–952 (1999).
Hsu, M., Andl, T., Li, G., Meinkoth, J. L. & Herlyn, M. Cadherin repertoire determines partner-specific gap junctional communication during melanoma progression. J. Cell Sci. 113, 1535–1542 (2000).
Moll, R., Mitze, M., Frixen, U. H. & Birchmeier, W. Differential loss of E-cadherin expression in infiltrating ductal and lobular breast carcinomas. Am. J. Pathol. 143, 1731–1742 (1993).
Klein, C. E., Steinmayer, T., Kaufmann, D., Weber, L. & Brocker, E. B. Identification of a melanoma progression antigen as integrin VLA-2. J. Invest. Dermatol. 96, 281–284 (1991).
Trikha, M. et al. The high affinity alphaIIb beta3 integrin is involved in invasion of human melanoma cells. Cancer Res. 57, 2522–2528 (1997).
Strobel, T. & Cannistra, S. A. Beta1-integrins partly mediate binding of ovarian cancer cells to peritoneal mesothelium in vitro. Gynecol. Oncol. 73, 362–367 (1999).
Chao, C., Lotz, M. M., Clarke, A. C. & Mercurio, A. M. A function for the integrin alpha6beta4 in the invasive properties of colorectal carcinoma cells. Cancer Res. 56, 4811–4819 (1996).
Cress, A. E., Rabinovitz, I., Zhu, W. & Nagle, R. B. The alpha 6 beta 1 and alpha 6 beta 4 integrins in human prostate cancer progression. Cancer Metastasis Rev. 14, 219–228 (1995).
Danen, E. H. J. et al. Regulation of integrin-mediated adhesion to laminin and collagen in human melanocytes and in non-metastatic and highly metastatic human melanoma cells. Int. J. Cancer 54, 315–321 (1993).
Zutter, M. M., Santoro, S. A., Staatz, W. D. & Tsung, Y. L. Re-expression of the alpha 2 beta 1 integrin abrogates the malignant phenotype of breast carcinoma cells. Proc. Natl Acad. Sci. USA 92, 7411–7415 (1995).
Schirner, M. et al. Integrin alpha5beta1: a potent inhibitor of experimental lung metastasis. Clin. Exp. Metastasis 16, 427–435 (1998).
Mignatti, P., Robbins, E. & Rifkin, D. B. Tumor invasion through the human amniotic membrane: requirement for a proteinase cascade. Cell 47, 487–498 (1986).
Kurschat, P. et al. Tissue inhibitor of matrix metalloproteinase-2 regulates matrix metalloproteinase-2 activation by modulation of membrane-type 1 matrix metalloproteinase activity in high and low invasive melanoma cell lines. J. Biol. Chem. 274, 21056–21062 (1999).
Ntayi, C., Lorimier, S., Berthier-Vergnes, O., Hornebeck, W. & Bernard, P. Cumulative influence of matrix metalloproteinase-1 and -2 in the migration of melanoma cells within three-dimensional type I collagen lattices. Exp. Cell Res. 270, 110–118 (2001).
Hotary, K., Allen, E., Punturieri, A., Yana, I. & Weiss, S. J. Regulation of cell invasion and morphogenesis in a three-dimensional type I collagen matrix by membrane-type matrix metalloproteinases 1, 2, and 3. J. Cell Biol. 149, 1309–1323 (2000). Together with references 63 and 159, this paper shows that MT1-MMP is the most important collagenase in invading tumour cells. They formally prove the concept that pericellular proteolysis contributes to invasion.
Wang, X., Fu, X., Brown, P. D., Crimmin, M. J. & Hoffman, R. M. Matrix metalloproteinase inhibitor BB-94 (batimastat) inhibits human colon tumor growth and spread in a patient-like orthotopic model in nude mice. Cancer Res. 54, 4726–4728 (1994).
Maki, H. et al. Augmented anti-metastatic efficacy of a selective matrix metalloproteinase inhibitor, MMI-166, in combination with CPT-11. Clin. Exp. Metastasis 19, 519–526 (2002).
Kruger, A. et al. Hydroxamate-type matrix metalloproteinase inhibitor batimastat promotes liver metastasis. Cancer Res. 61, 1272–1275 (2001).
Della, P. P. et al. Combined treatment with serine protease inhibitor aprotinin and matrix metalloproteinase inhibitor Batimastat (BB-94) does not prevent invasion of human esophageal and ovarian carcinoma cells in vivo. Anticancer Res. 19, 3809–3816 (1999).
Zucker, S., Cao, J. & Chen, W. T. Critical appraisal of the use of matrix metalloproteinase inhibitors in cancer treatment. Oncogene 19, 6642–6650 (2000).
Coussens, L. M., Fingleton, B. & Matrisian, L. M. Matrix metalloproteinase inhibitors and cancer: trials and tribulations. Science 295, 2387–2392 (2002).
Overall, C. M. & Lopez-Otin, C. Strategies for MMP inhibition in cancer: innovations for the post-trial era. Nature Rev. Cancer 2, 657–672 (2002). References 127–129 summarize and explain the failure of clinical trials of matrix metalloproteinase inhibitors in late-stage cancer patients. It sets the scene for future work in the MMP field.
Lochter, A., Navre, M., Werb, Z. & Bissell, M. J. alpha1 and alpha2 integrins mediate invasive activity of mouse mammary carcinoma cells through regulation of stromelysin-1 expression. Mol. Biol. Cell 10, 271–282 (1999).
Sternlicht, M. D. & Werb, Z. How matrix metalloproteinases regulate cell behavior. Annu. Rev. Cell Dev. Biol. 17, 463–516 (2001).
Sakkab, D. et al. Signaling of hepatocyte growth factor/scatter factor (HGF) to the small GTPase Rap1 via the large docking protein Gab1 and the adapter protein CRKL. J. Biol. Chem. 275, 10772–10778 (2000).
Quirt, I. et al. Phase II study of marimastat (BB-2516) in malignant melanoma: a clinical and tumor biopsy study of the National Cancer Institute of Canada Clinical Trials Group. Invest. New Drugs 20, 431–437 (2002).
Bonomi, P. Matrix metalloproteinases and matrix metalloproteinase inhibitors in lung cancer. Semin. Oncol. 29, 78–86 (2002).
Harbeck, N., Kates, R. E. & Schmitt, M. Clinical relevance of invasion factors urokinase-type plasminogen activator and plasminogen activator inhibitor type 1 for individualized therapy decisions in primary breast cancer is greatest when used in combination. J. Clin. Oncol. 20, 1000–1007 (2002).
Leung-Toung, R., Li, W., Tam, T. F. & Karimian, K. Thiol-dependent enzymes and their inhibitors: a review. Curr. Med. Chem. 9, 979–1002 (2002).
Fassler, R. & Meyer, M. Consequences of lack of beta 1 integrin gene expression in mice. Genes Dev. 9, 1896–1908 (1995).
Fassler, R. et al. Lack of beta 1 integrin gene in embryonic stem cells affects morphology, adhesion, and migration but not integration into the inner cell mass of blastocysts. J. Cell Biol. 128, 979–988 (1995). Together with references 35, 76 and 77, this paper shows that β1 integrins can be dispensable for cell movement and positioning in 3D tissue structures.
Lombardi, L. et al. Ultrastructural cytoskeleton alterations and modification of actin expression in the NIH/3T3 cell line after transformation with Ha-ras-activated oncogene. Cell Motil. Cytoskeleton 15, 220–229 (1990).
Dartsch, P. C., Ritter, M., Haussinger, D. & Lang, F. Cytoskeletal reorganization in NIH 3T3 fibroblasts expressing the Ras oncogene. Eur. J. Cell Biol. 63, 316–325 (1994).
Khosravi-Far, R. et al. Dbl and Vav mediate transformation via mitogen-activated protein kinase pathways that are distinct from those activated by oncogenic Ras. Mol. Cell. Biol. 14, 6848–6857 (1994).
Qiu, R. G., Chen, J., McCormick, F. & Symons, M. A role for Rho in Ras transformation. Proc. Natl Acad. Sci. USA 92, 11781–11785 (1995).
Whittard, J. D. & Akiyama, S. K. Activation of beta1 integrins induces cell–cell adhesion. Exp. Cell Res. 263, 65–76 (2001).
Robinson, E. E., Zazzali, K. M., Corbett, S. A. & Foty, R. A. Alpha5beta1 integrin mediates strong tissue cohesion. J. Cell Sci. 116, 377–386 (2003).
Whittard, J. D. et al. E-cadherin is a ligand for integrin alpha2beta1. Matrix Biol. 21, 525–532 (2002).
Hynes, R. O. & Zhao, Q. The evolution of cell adhesion. J. Cell Biol. 150, F89–F96 (2000). Insightful overview of how adhesion receptors evolved in the context of increasing tissue complexity and segregation.
Blanchoin, L. et al. Direct observation of dendritic actin filament networks nucleated by Arp2/3 complex and WASP/Scar proteins. Nature 404, 1007–1011 (2000).
Nobes, C. D. & Hall, A. Rho, Rac, and Cdc42 GTPases regulate the assembly of multimolecular focal complexes associated with actin stress fibers, lamellipodia, and filopodia. Cell 81, 53–62 (1995).
Ren, X. D. et al. Physical association of the small GTPase Rho with a 68-kDa phosphatidylinositol 4-phosphate 5-kinase in Swiss 3T3 cells. Mol. Biol. Cell 7, 435–442 (1996).
Leopoldt, D. et al. Gbetagamma stimulates phosphoinositide 3-kinase-gamma by direct interaction with two domains of the catalytic p110 subunit. J. Biol. Chem. 273, 7024–7029 (1998).
Tsutsumi, S., Gupta, S. K., Hogan, V., Collard, J. G. & Raz, A. Activation of small GTPase Rho is required for autocrine motility factor signaling. Cancer Res. 62, 4484–4490 (2002).
Miyamoto, S. et al. Integrin function: molecular hierarchies of cytoskeletal and signaling molecules. J. Cell Biol. 131, 791–805 (1995).
Calderwood, D. A., Shattil, S. J. & Ginsberg, M. H. Integrins and actin filaments: reciprocal regulation of cell adhesion and signaling. J. Biol. Chem. 275, 22607–22610 (2000).
Degani, S. et al. The integrin cytoplasmic domain-associated protein ICAP-1 binds and regulates Rho family GTPases during cell spreading. J. Cell Biol. 156, 377–387 (2002).
DeMali, K. A., Barlow, C. A. & Burridge, K. Recruitment of the Arp2/3 complex to vinculin: coupling membrane protrusion to matrix adhesion. J. Cell Biol. 159, 881–891 (2002).
Schwartz, M. A. & Shattil, S. J. Signaling networks linking integrins and Rho family GTPases. Trends Biochem. Sci. 25, 388–391 (2000).
Ilic, D. et al. Reduced cell motility and anhanced focal adhesion contact formation in cells from FAK-deficient mice. Nature 377, 539–544 (1995).
Mueller, S. C. et al. A novel protease-docking function of integrin at invadopodia. J. Biol. Chem. 274, 24947–24952 (1999).
Ohuchi, E. et al. Membrane type 1 matrix metalloproteinase digests interstitial collagens and other extracellular matrix macromolecules. J. Biol. Chem. 272, 2446–2451 (1997).
Dumin, J. A. et al. Pro-collagenase-1 (matrix metalloproteinase-1) binds the alpha(2)beta(1) integrin upon release from keratinocytes migrating on type I collagen. J. Biol. Chem. 276, 29368–29374 (2001).
Brooks, P. C., Silletti, S., von Schalscha, T. L., Friedlander, M. & Cheresh, D. A. Disruption of angiogenesis by PEX, a noncatalytic metalloproteinase fragment with integrin binding activity. Cell 92, 391–400 (1998).
Ellerbroek, S. M., Wu, Y. I., Overall, C. M. & Stack, M. S. Functional interplay between type I collagen and cell surface matrix metalloproteinase activity. J. Biol. Chem. 276, 24833–24842 (2001).
Galvez, B. G., Matias-Roman, S., Yanez-Mo, M., Sanchez-Madrid, F. & Arroyo, A. G. ECM regulates MT1-MMP localization with beta1 or alphavbeta3 integrins at distinct cell compartments modulating its internalization and activity on human endothelial cells. J. Cell Biol. 159, 509–521 (2002).
Tam, E. M., Wu, Y. I., Butler, G. S., Stack, M. S. & Overall, C. M. Collagen binding properties of the membrane type-1 matrix metalloproteinase (MT1-MMP) hemopexin C domain. The ectodomain of the 44-kDa autocatalytic product of MT1-MMP inhibits cell invasion by disrupting native type I collagen cleavage. J. Biol. Chem. 277, 39005–39014 (2002).
Fukata, Y., Amano, M. & Kaibuchi, K. Rho-Rho-kinase pathway in smooth muscle contraction and cytoskeletal reorganization of non-muscle cells. Trends Pharmacol. Sci. 22, 32–39 (2001).
Wear, M. A., Schafer, D. A. & Cooper, J. A. Actin dynamics: assembly and disassembly of actin networks. Curr. Biol. 10, R891–R895 (2000).
Zeng, L. et al. PTP alpha regulates integrin-stimulated FAK autophosphorylation and cytoskeletal rearrangement in cell spreading and migration. J. Cell Biol. 160, 137–146 (2003).
Pfaff, M., Du, X. & Ginsberg, M. H. Calpain cleavage of integrin beta cytoplasmic domains. FEBS Lett. 460, 17–22 (1999).
Moss, M. L. & Lambert, M. H. Shedding of membrane proteins by ADAM family proteases. Essays Biochem. 38, 141–153 (2002).
Carragher, N. O., Levkau, B., Ross, R. & Raines, E. W. Degraded collagen fragments promote rapid disassembly of smooth muscle focal adhesions that correlates with cleavage of pp125(FAK), paxillin, and talin. J. Cell Biol. 147, 619–630 (1999).
Bretscher, M. S. Getting membrane flow and the cytoskeleton to cooperate in moving cells. Cell 87, 601–606 (1996).
Firtel, R. A. & Meili, R. Dictyostelium: a model for regulated cell movement during morphogenesis. Curr. Opin. Genet. Dev. 10, 421–427 (2000).
Scotton, C. J. et al. Multiple actions of the chemokine CXCL12 on epithelial tumor cells in human ovarian cancer. Cancer Res. 62, 5930–5938 (2002).
Price, J. T., Tiganis, T., Agarwal, A., Djakiew, D. & Thompson, E. W. Epidermal growth factor promotes MDA-MB-231 breast cancer cell migration through a phosphatidylinositol 3′-kinase and phospholipase C-dependent mechanism. Cancer Res. 59, 5475–5478 (1999).
Sawada, K. et al. Alendronate inhibits lysophosphatidic acid-induced migration of human ovarian cancer cells by attenuating the activation of Rho. Cancer Res. 62, 6015–6020 (2002).
Doerr, M. E. & Jones, J. I. The roles of integrins and extracellular matrix proteins in the insulin-like growth factor 1-stimulated chemotaxis of human breast cancer cells. J. Biol. Chem. 271, 2443–2447 (1996).
Invasion and metastasis
A key feature that distinguishes cancer cells from all other cells is the capability to spread throughout the body by two related mechanisms: invasion and metastasis.
Invasion
Invasion refers to the direct extension and penetration by cancer cells into neighbouring tissues. The proliferation of transformed cells and the progressive increase in tumour size eventually leads to a breach in the barriers between tissues, leading to tumour extension into adjacent tissue. Local invasion is also the first stage in the process that leads to the development of secondary tumours or metastases.4, 7, 10
Metastasis
Metastasis, from the Greek methistanai, meaning to move to another place, describes the ability of cancer cells to penetrate into lymphatic and blood vessels, circulate through these systems and invade normal tissues elsewhere in the body. This process proceeds in an orderly and predictable manner, sometimes termed the ‘metastatic cascade’.4, 7, 10
The ability of cancer cells to migrate from a primary site of disease is attributed to the mutation of genes that regulate the production of proteins that normally tether cells to their surrounding tissues. Decreased synthesis by cancer cells of a number of substances that bind them to neighbouring cells, together with the abnormal synthesis of enzymes capable of degrading the bonds between cells and tissues, allow cancer cells to escape the primary tumour site.4, 7, 10
Angiogenesis
Angiogenesis has a role in tumour growth, invasiveness and metastasis.32, 33 Tumour angiogenesis refers to the growth of new vessels which develop following stimulation of endothelial cells within existing vascular networks near the tumour, providing a blood supply for that tumour.33 A balance of stimulators and inhibitors tightly control angiogenesis under normal circumstances.2, 26 One specific and potent promoter of angiogenesis is vascular endothelial growth factor (VEGF).26
Vascular endothelial growth factor (VEGF)
VEGF is a cytokine which exerts its effects on vascular endothelial cells promoting the formation of new blood vessels and is critical to both normal and tumour angiogenesis:26, 34 VEGF is over-expressed in a variety of solid tumours and certain hematologic malignancies. VEGF action involves:26
binding to and activating two structurally related membrane receptor tyrosine kinases (TKs)
switching on of multiple signaling pathways
stimulating the growth, survival, and proliferation of vascular endothelial cells
promoting tumour growth and contributing to tumour invasion and metastasis.
Tyrosine kinases (TK)
Tumour growth and progression is further reliant on the activity of specific cell membrane receptors which control signaling pathways within the cell. Cell signaling or ‘signal transduction’ involves the communication process where messages or signals from outside the cell are transferred to the nucleus inside the cell.26 Tyrosine kinases (TK) are a subgroup of growth receptors involved in the signal transduction process.26 Because TKs are regulators of the signal transduction process, they play a role in cellular processes such as proliferation, migration, metabolism, differentiation and survival.26 Several important growth factors and other TKs have been identified:26
EGFR family
platelet derived growth factor receptor (PDGF)
BCR-ABL
KIT
vascular endothelial growth factor (VEGF)
transforming growth factor (TGF)
fibroblast growth factor (FGF).
Learning activities
Access a current text and map the stages of the metastatic cascade, explaining the events in the development of metastases.
Distinguish between the different members of the EGFRs family.
Apart from EGFR components of the TKs involved in signal transduction, list two other TK receptors and the specific cancer they are expressed in.
Distinguish between the different members of the VEGF receptors, including the receptor which leads to the development of anti-angiogenic agents in cancer therapy.
Next: Cancer signs and symptoms
Cell migration
Regulated self-propelled movement of cells from one site to another guided by molecular cues
Cell migration is a central process in the development and maintenance of multicellular organisms. Tissue formation during embryonic development, wound healing and immune responses all require the orchestrated movement of cells in particular directions to specific locations. Cells often migrate in response to specific external signals, including chemical signals and mechanical signals.[1] Errors during this process have serious consequences, including intellectual disability, vascular disease, tumor formation and metastasis. An understanding of the mechanism by which cells migrate may lead to the development of novel therapeutic strategies for controlling, for example, invasive tumour cells.
Due to the highly viscous environment (low Reynolds number), cells need to continuously produce forces in order to move. Cells achieve active movement by very different mechanisms. Many less complex prokaryotic organisms (and sperm cells) use flagella or cilia to propel themselves. Eukaryotic cell migration typically is far more complex and can consist of combinations of different migration mechanisms. It generally involves drastic changes in cell shape which are driven by the cytoskeleton. Two very distinct migration scenarios are crawling motion (most commonly studied) and blebbing motility.[2][3] A paradigmatic example of crawling motion is the case of fish epidermal keratocytes, which have been extensively used in research and teaching.[4]
Cell migration studies [ edit ]
The migration of cultured cells attached to a surface or in 3D is commonly studied using microscopy.[5][6][3] As cell movement is very slow, a few µm/minute, time-lapse microscopy videos are recorded of the migrating cells to speed up the movement. Such videos (Figure 1) reveal that the leading cell front is very active, with a characteristic behavior of successive contractions and expansions. It is generally accepted that the leading front is the main motor that pulls the cell forward.
Common features [ edit ]
The processes underlying mammalian cell migration are believed to be consistent with those of (non-spermatozooic) locomotion.[7] Observations in common include:
cytoplasmic displacement at leading edge (front)
laminar removal of dorsally-accumulated debris toward trailing edge (back)
The latter feature is most easily observed when aggregates of a surface molecule are cross-linked with a fluorescent antibody or when small beads become artificially bound to the front of the cell.[8]
Other eukaryotic cells are observed to migrate similarly. The amoeba Dictyostelium discoideum is useful to researchers because they consistently exhibit chemotaxis in response to cyclic AMP; they move more quickly than cultured mammalian cells; and they have a haploid genome that simplifies the process of connecting a particular gene product with its effect on cellular behaviour.[9]
Two different models for how cells move. A) Cytoskeletal model. B) Membrane Flow Model
(A) Dynamic microtubules are necessary for tail retraction and are distributed at the rear end in a migrating cell. Green, highly dynamic microtubules; yellow, moderately dynamic microtubules and red, stable microtubules. (B) Stable microtubules act as struts and prevent tail retraction and thereby inhibit cell migration.
Molecular processes of migration [ edit ]
There are two main theories for how the cell advances its front edge: the cytoskeletal model and membrane flow model. It is possible that both underlying processes contribute to cell extension.
Cytoskeletal model (A) [ edit ]
Leading edge [ edit ]
Experimentation has shown that there is rapid actin polymerisation at the cell’s front edge.[10] This observation has led to the hypothesis that formation of actin filaments “push” the leading edge forward and is the main motile force for advancing the cell’s front edge.[11][12] In addition, cytoskeletal elements are able to interact extensively and intimately with a cell’s plasma membrane.[13]
Trailing edge [ edit ]
Other cytoskeletal components (like microtubules) have important functions in cell migration. It has been found that microtubules act as “struts” that counteract the contractile forces that are needed for trailing edge retraction during cell movement. When microtubules in the trailing edge of cell are dynamic, they are able to remodel to allow retraction. When dynamics are suppressed, microtubules cannot remodel and, therefore, oppose the contractile forces.[14] The morphology of cells with suppressed microtubule dynamics indicate that cells can extend the front edge (polarized in the direction of movement), but have difficulty retracting their trailing edge.[15] On the other hand, high drug concentrations, or microtubule mutations that depolymerize the microtubules, can restore cell migration but there is a loss of directionality. It can be concluded that microtubules act both to restrain cell movement and to establish directionality.
Membrane flow model (B) [ edit ]
The front of a migrating cell is also the site at which the membrane from internal membrane pools is returned to the cell surface at the end of the endocytic cycle.[16] [17] This suggests that extension of the leading edge occurs primarily by addition of membrane at the front of the cell. If so, the actin filaments that form there might stabilize the added membrane so that a structured extension, or lamella, is formed — rather than a bubble-like structure (or bleb) at its front.[18] For a cell to move, it is necessary to bring a fresh supply of “feet” (proteins called integrins, which attach a cell to the surface on which it is crawling) to the front. It is likely that these feet are endocytosed [19] toward the rear of the cell and brought to the cell’s front by exocytosis, to be reused to form new attachments to the substrate.
In the case of Dictyostelium amoebae, three conditional temperature sensitive mutants which affect membrane recycling block cell migration at the restrictive (higher) temperature;[20][21][22] they provide additional support for the importance of the endocytic cycle in cell migration. Furthermore, these amoebae move quite quickly — about one cell length in ~5 mins. If they are regarded as cylindrical (which is roughly true whilst chemotaxing), this would require them to recycle the equivalent of one cell surface area each 5 mins, which is approximately what is measured.[23] [24] Rearward membrane flow (red arrows) and vesicle trafficking from back to front (blue arrows) drive adhesion-independent migration.
Mechanistic basis of amoeboid migration [ edit ]
Adhesive crawling is not the only migration mode exhibited by eukaryotic cells. Importantly, several cell types — Dictyostelium amoebae, neutrophils, metastatic cancer cells and macrophages — have been found to be capable of adhesion-independent migration. Historically, the physicist E. M. Purcell theorized (in 1977) that under conditions of low Reynolds number fluid dynamics, which apply at the cellular scale, rearward surface flow could provide a mechanism for microscopic objects to swim forward.[25] After some decades, experimental support for this model of cell movement was provided when it was discovered (in 2010) that amoeboid cells and neutrophils are both able to chemotax towards a chemo-attractant source whilst suspended in an isodense medium.[26] It was subsequently shown, using optogenetics, that cells migrating in an amoeboid fashion without adhesions exhibit plasma membrane flow towards the cell rear that may propel cells by exerting tangential forces on the surrounding fluid.[24][27] Polarized trafficking of membrane-containing vesicles from the rear to the front of the cell helps maintain cell size.[24] Rearward membrane flow was also observed in Dictyostelium discoideum cells.[28] These observations provide strong support for models of cell movement which depend on a rearward cell surface membrane flow (Model B, above). Interestingly, the migration of supracellular clusters has also been found to be supported by a similar mechanism of rearward surface flow.[29] [30] Schematic representation of the collective biomechanical and molecular mechanism of cell motion
Collective biomechanical and molecular mechanism of cell motion [ edit ]
Based on some mathematical models, recent studies hypothesize a novel biological model for collective biomechanical and molecular mechanism of cell motion.[30] It is proposed that microdomains weave the texture of cytoskeleton and their interactions mark the location for formation of new adhesion sites. According to this model, microdomain signaling dynamics organizes cytoskeleton and its interaction with substratum. As microdomains trigger and maintain active polymerization of actin filaments, their propagation and zigzagging motion on the membrane generate a highly interlinked network of curved or linear filaments oriented at a wide spectrum of angles to the cell boundary. It is also proposed that microdomain interaction marks the formation of new focal adhesion sites at the cell periphery. Myosin interaction with the actin network then generate membrane retraction/ruffling, retrograde flow, and contractile forces for forward motion. Finally, continuous application of stress on the old focal adhesion sites could result in the calcium-induced calpain activation, and consequently the detachment of focal adhesions which completes the cycle.
Polarity in migrating cells [ edit ]
Migrating cells have a polarity—a front and a back. Without it, they would move in all directions at once, i.e. spread. How this polarity is formulated at a molecular level inside a cell is unknown. In a cell that is meandering in a random way, the front can easily give way to become passive as some other region, or regions, of the cell form(s) a new front. In chemotaxing cells, the stability of the front appears enhanced as the cell advances toward a higher concentration of the stimulating chemical. This polarity is reflected at a molecular level by a restriction of certain molecules to particular regions of the inner cell surface. Thus, the phospholipid PIP3 and activated Rac and CDC42 are found at the front of the cell, whereas Rho GTPase and PTEN are found toward the rear.[31][32]
It is believed that filamentous actins and microtubules are important for establishing and maintaining a cell’s polarity.[citation needed] Drugs that destroy actin filaments have multiple and complex effects, reflecting the wide role that these filaments play in many cell processes. It may be that, as part of the locomotory process, membrane vesicles are transported along these filaments to the cell’s front. In chemotaxing cells, the increased persistence of migration toward the target may result from an increased stability of the arrangement of the filamentous structures inside the cell and determine its polarity. In turn, these filamentous structures may be arranged inside the cell according to how molecules like PIP3 and PTEN are arranged on the inner cell membrane. And where these are located appears in turn to be determined by the chemoattractant signals as these impinge on specific receptors on the cell’s outer surface.
Although microtubules have been known to influence cell migration for many years, the mechanism by which they do so has remained controversial. On a planar surface, microtubules are not needed for the movement, but they are required to provide directionality to cell movement and efficient protrusion of the leading edge.[15][33] When present, microtubules retard cell movement when their dynamics are suppressed by drug treatment or by tubulin mutations.[15]
Inverse problems in the context of cell motility [ edit ]
An area of research called inverse problems in cell motility has been established. [34][35][30] This approach is based on the idea that behavioral or shape changes of a cell bear information about the underlying mechanisms that generate these changes. Reading cell motion, namely, understanding the underlying biophysical and mechanochemical processes, is of paramount importance. [36] [37] The mathematical models developed in these works determine some physical features and material properties of the cells locally through analysis of live cell image sequences and uses this information to make further inferences about the molecular structures, dynamics, and processes within the cells, such as the actin network, microdomains, chemotaxis, adhesion, and retrograde flow.
See also [ edit ]
References [ edit ]
Tumour-cell invasion and migration: Diversity and escape mechanisms
TY – JOUR
T1 – Tumour-cell invasion and migration
T2 – Diversity and escape mechanisms
AU – Friedl, Peter
AU – Wolf, Katarina
N1 – Funding Information: We gratefully acknowledge E.-B. Bröcker for continuous support. The work from the authors’ laboratory is supported by current or previous grants from the Deutsche Forschungsgemeinschaft, the Ministry for Education and Research, the Wilhelm-Sander Foundation, Evangelisches Studienwerk e.V., Haus Villigst and the Interdisciplinary Center for Clinical Research (IZKF), Würzburg.
PY – 2003/5
Y1 – 2003/5
N2 – Cancer cells possess a broad spectrum of migration and invasion mechanisms. These include both individual and collective cell-migration strategies. Cancer therapeutics that are designed to target adhesion receptors or proteases have not proven to be effective in slowing tumour progression in clinical trials – this might be due to the fact that cancer cells can modify their migration mechanisms in response to different conditions. Learning more about the cellular and molecular basis of these different migration/invasion programmes will help us to understand how cancer cells disseminate and lead to new treatment strategies.
AB – Cancer cells possess a broad spectrum of migration and invasion mechanisms. These include both individual and collective cell-migration strategies. Cancer therapeutics that are designed to target adhesion receptors or proteases have not proven to be effective in slowing tumour progression in clinical trials – this might be due to the fact that cancer cells can modify their migration mechanisms in response to different conditions. Learning more about the cellular and molecular basis of these different migration/invasion programmes will help us to understand how cancer cells disseminate and lead to new treatment strategies.
UR – http://www.scopus.com/inward/record.url?scp=0038049137&partnerID=8YFLogxK
UR – http://www.scopus.com/inward/citedby.url?scp=0038049137&partnerID=8YFLogxK
U2 – 10.1038/nrc1075
DO – 10.1038/nrc1075
M3 – Review article
C2 – 12724734
AN – SCOPUS:0038049137
VL – 3
SP – 362
EP – 374
JO – Nature Reviews Cancer
JF – Nature Reviews Cancer
SN – 1474-175X
IS – 5
ER –
Tumour-cell invasion and migration: diversity and escape mechanisms
JavaScript is not enabled in your browser.
To use Dimensions, please enable JavaScript in the options of your browser or talk to your local administrator.
Tumour-cell invasion and migration: diversity and escape mechanisms
Cancer cells possess a broad spectrum of migration and invasion mechanisms. These include both individual and collective cell-migration strategies. Cancer therapeutics that are designed to target adhesion receptors or proteases have not proven to be effective in slowing tumour progression in clinical trials — this might be due to the fact that cancer cells can modify their migration mechanisms in response to different conditions. Learning more about the cellular and molecular basis of these… Expand
키워드에 대한 정보 tumour cell invasion and migration diversity and escape mechanisms
다음은 Bing에서 tumour cell invasion and migration diversity and escape mechanisms 주제에 대한 검색 결과입니다. 필요한 경우 더 읽을 수 있습니다.
이 기사는 인터넷의 다양한 출처에서 편집되었습니다. 이 기사가 유용했기를 바랍니다. 이 기사가 유용하다고 생각되면 공유하십시오. 매우 감사합니다!
사람들이 주제에 대해 자주 검색하는 키워드 Introduction to Cancer Biology (Part 3): Tissue Invasion and Metastasis
- Metastasis
- Cancer
- Invasion
- Tissue
Introduction #to #Cancer #Biology #(Part #3): #Tissue #Invasion #and #Metastasis
YouTube에서 tumour cell invasion and migration diversity and escape mechanisms 주제의 다른 동영상 보기
주제에 대한 기사를 시청해 주셔서 감사합니다 Introduction to Cancer Biology (Part 3): Tissue Invasion and Metastasis | tumour cell invasion and migration diversity and escape mechanisms, 이 기사가 유용하다고 생각되면 공유하십시오, 매우 감사합니다.
