Hostname: page-component-7dd5485656-frp75 Total loading time: 0 Render date: 2025-10-30T05:34:10.780Z Has data issue: false hasContentIssue false
  • English
  • Français

Intracellular Modelling of Cell-Matrix Adhesion during CancerCell Invasion

Published online by Cambridge University Press:  25 January 2012

V. Andasari  and
M.A.J. Chaplain
Get access

Abstract

When invading the tissue, malignant tumour cells (i.e. cancer cells) need to detach fromneighbouring cells, degrade the basement membrane, and migrate through the extracellularmatrix. These processes require loss of cell-cell adhesion and enhancement of cell-matrixadhesion. In this paper we present a mathematical model of an intracellular pathway forthe interactions between a cancer cell and the extracellular matrix. Cancer cells usesimilar mechanisms as with normal cells for their interactions with the extracellularmatrix. We develop a model of cell-matrix adhesion that accounts for reactions between thecell surface receptor integrins, the matrix glycoprotein fibronectin, and the actinfilaments in the cytoskeleton. Each represents components for an intermediate compartment,the extracellular compartment, and the intracellular compartment, respectively. Binding offibronectin with integrins triggers a clustering of protein complexes, which thenactivates and phosphorylates regulatory proteins that are involved in actin reorganisationcausing actin polymerization and stress fibre assembly. Rearrangement of actin filamentswith integrin/fibronectin complexes near adhesion sites and interaction with fibrillarfibronectin produces the force necessary for cell migration, accounting for cell-matrixadhesion.

Keywords

cancer invasioncell-matrix adhesionintegrinsfibronectinactin

Information

Type
Research Article
Information
Mathematical Modelling of Natural Phenomena , Volume 7 , Issue 1: Cancer modeling , 2012 , pp. 29 - 48
Copyright
© EDP Sciences, 2012

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Article purchase

Temporarily unavailable

References

Abraham, V.C., Krishnamurthi, V., Taylor, D.L., Lanni, F.. The actin-based nanomachine at the leading edge of migrating cells. Biophys. J., 77 (1999), No. 3, 1721–1732. CrossRefGoogle ScholarPubMed
Ali, O., Guillou, H., Destaing, O., Albiges-Rizo, C., Block, M.R., Fourcade, B.. Cooperativity between integrin activation and mechanical stress leads to integrin clustering. Biophys. J., 100 (2011), No. 11, 2595–2604. CrossRefGoogle ScholarPubMed
Amano, M., Chihara, K., Kimura, K., Fukata, Y., Nakamura, N., Matsuura, Y., Kaibuchi, K.. Formation of actin stress fibers and focal adhesions enhanced by rho-kinase. Science, 297 (1997), No. 5304, 1308–1311. CrossRefGoogle Scholar
Ananthakrishnan, R., Ehrlicher, A.. The force behind cell movement. Int. J. Biol. Sci., 3 (2007), No. 5, 303–317. CrossRefGoogle Scholar
Berrier, A.L., Yamada, K.M.. Cell-matrix adhesion. J. Cell. Physiol., 213 (2007), No. 3, 565–573. CrossRefGoogle ScholarPubMed
Butler, B., Gao, C., Mersich, A.T., Blystone, S.D.. Purified integrin adhesion complexes exhibit actin-polymerization activity. Curr. Biol., 16 (2006), No. 3, 242–251. CrossRefGoogle ScholarPubMed
Chen, L.L., Whitty, A., Lobb, R.R., Adams, S.P., Pepinsky, R.B.. Multiple activation states of integrin α4 β1 detected through their different affinities for a small molecule ligand. J. Biol. Chem., 274 (1999), No. 19, 13167–13175. CrossRefGoogle Scholar
Choquet, D., Felsenfeld, D.P., Sheetz, M.P.. Extracellular matrix rigidity causes strengthening of integrin-cytoskeleton linkages. Cell, 88 (1997), No. 1, 39–48. CrossRefGoogle ScholarPubMed
Cluzel, C., Saltel, F., Lussi, J., Paulhe, F., Imhof, B.A., Wehrle-Haller, B.. The mechanisms and dynamics of αvβ3 integrin clustering in living cells. J. Cell. Biol., 171 (2005), No. 2, 383–392. CrossRefGoogle Scholar
Cseh, B., Fernandez-Sauze, S., Grall, D., Schaub, S., Doma, E., van Obberghen-Schilling, E.. Autocrine fibronectin directs matrix assembly and crosstalk between cell-matrix and cell-cell adhesion in vascular endothelial cells. J. Cell Sci., 123 (2010), No. 22, 3989–3999. CrossRefGoogle ScholarPubMed
DiMilla, P.A., Barbee, K., Lauffenburger, D.A.. Mathematical model for the effects of adhesion and mechanics on cell migration speed. Biophys. J., 60 (1991), No. 1, 15–37. CrossRefGoogle ScholarPubMed
Doherty, G.J., Ahlund, M.K., Howes, M.T., Moren, B., Parton, R.G., McMahon, H.T., Lundmark, R.. The endocytic protein GRAF1 is directed to cell-matrix adhesion sites and regulates cell spreading. Mol. Biol. Cell, 22 (2011), No. 22, 4380–4389. CrossRefGoogle ScholarPubMed
Friedl, P., Wolf, K.. Tumour-cell invasion and migration : diversity and escape mechanisms. Nat. Rev. Cancer, 3 (2003), No. 5, 362–374. CrossRefGoogle Scholar
Fussenegger, M., Bailey, J.E., Varner, J.. A mathematical model of caspase function in apoptosis. Nat. Biotechnol., 18 (2000), 768–774. CrossRefGoogle ScholarPubMed
Gallant, N.D., Michael, K.E., García, A.J.. Cell adhesion strengthening : contributions of adhesive area, integrin binding, and focal adhesion assembly. Mol. Biol. Cell, 16 (2005), No. 9, 4329–4340. CrossRefGoogle ScholarPubMed
García, A.J., Boettiger, D.. Integrin-fibronectin interactions at the cell-material interface : initial integrin binding and signaling. Biomaterials, 20 (1999), No. 23–24, 2427–2433. CrossRefGoogle Scholar
García, A.J., Huber, F., Boettiger, D.. Force required to break α5β1 integrin-fibronectin bonds in intact adherent cells is sensitive to integrin activation state. J. Biol. Chem., 273 (1998), No. 18, 10988–10993. CrossRefGoogle ScholarPubMed
Giancotti, F.G., Ruoslahti, E.. Integrin signaling. Science, 285 (1999), No. 5430, 1028–1032. CrossRefGoogle ScholarPubMed
Gilcrease, M.Z., Zhou, X., Welch, K.. Adhesion-independent α6β4 integrin clustering is mediated by phosphatidylinositol 3-kinase. Cancer Res., 64 (2004), 7395. CrossRefGoogle ScholarPubMed
Guo, W.H., Wang, Y.L.. Retrograde fluxes of focal adhesion proteins in response to cell migration and mechanical signals. Mol. Biol. Cell, 18 (2007), No. 11, 4519–4527. CrossRefGoogle ScholarPubMed
Hammer, D.A., Lauffenburger, D.A.. A dynamical model for receptor-mediated cell adhesion to surfaces. Biophys. J., 53 (1987), No. 3, 475–487. CrossRefGoogle Scholar
Hynes, R.O.. Integrins : bidirectional, allosteric signaling machines. Cell, 110 (2002), No. 6, 673–687. CrossRefGoogle ScholarPubMed
Kawakami, K., Tatsumi, H., Sokabe, M.. Dynamics of integrin clustering at focal contacts of endothelial cells studied by multimode imaging microscopy. J. Cell Sci., 114 (2001), No. 17, 3125–3135. Google ScholarPubMed
P. Koistinen, J. Heino. Integrins in cancer cell invasion. Cell invasion. Landes Bioscience, 2002.
Li, Z.H., Kreiner, M., van der Walle, C.F., Mardon, H.J.. Clustered integrin alpha-5-beta-1 ligand displays model fibronectin-mediated adhesion of human endometrial stromal cells. Biochem. Biophys. Res. Comm., 407 (2011), No. 4, 777–782. CrossRefGoogle ScholarPubMed
Machesky, L.M., Hall, A.. Role of actin polymerization and adhesion to extracellular matrix in Rac-and Rho-induced cytoskeletal reorganization. J. Cell. Biol., 138 (1997), No. 4, 913–926. CrossRefGoogle Scholar
Mallavarapu, A., Mitchison, T.. Regulated actin cytoskeleton assembly at filopodium tips controls their extension and retraction. J. Cell. Biol., 146 (1999), No. 5, 1097–1106. CrossRefGoogle Scholar
Martini, M., Gnann, A., Scheiki, D., Holzmann, B., Janssen, K.P.. The candidate tumor suppressor SASH1 interacts with the actin cytoskeleton and stimulates cell-matrix adhesion. Int. J. Biochem. Cell. Biol., 43 (2011), No. 11, 1630–1640. CrossRefGoogle ScholarPubMed
Monaghan, E., Gueorguiev, V., Wilkins-Port, C.. The receptor for urokinase-type plasminogen activator regulates fibronectin matrix assembly in human skin fibroblasts. J. Biol. Chem., 279 (2004), No. 2, 1400–1407. CrossRefGoogle ScholarPubMed
Moretti, F.A., Chauhan, A.K., Iaconcig, A., Porro, F., Baralle, F.E., Muro, A.F.. A major fraction of fibronectin present in the extracellular matrix of tissues is plasma-derived. J. Biol. Chem., 282 (2007), No. 38, 28057–28062. CrossRefGoogle Scholar
S. Niland, J.A. Eble. Integrin-mediated cell-matrix interaction in physiological and pathological blood vessel formation. J. Oncol., (2012), Epub 2011 Sep 18, 125278.
Nishizaka, T., Shi, Q., Sheetz, M.P.. Position-dependent linkages of fibronectin-integrin-cytoskeleton. PNAS, 97 (2000), No. 2, 692–697. CrossRefGoogle ScholarPubMed
Ojaniemi, M., Vuori, K.. Epidermal growth factor modulates tyrosine phosphorylation of p130Cas. Involvement of phophatidylinositol 3’-kinase and actin cytoskeleton. J. Biol. Chem., 272 (1997), No. 41, 25993–25998. CrossRefGoogle Scholar
Osada, T., Gu, Y.H., Kanazawa, M., Tsubota, Y., Hawkins, B.T., Spatz, M., Milner, R., del Zoppo, G.J.. Interendothelial claudin-5 expression depends on cerebral endothelial cell-matrix adhesion by beta(1)-integrins. J. Cereb. Blood Flow Metab., 31 (2011), No. 10, 1972–1985. CrossRefGoogle Scholar
Palecek, S.P., Horwitz, A.F., Lauffenburger, D.A.. Kinetic model for integrin-mediated adhesion release during cell migration. Ann. Biomed. Eng., 27 (1999), No. 2, 219–235. CrossRefGoogle ScholarPubMed
Palecek, S.P., Huttenlocher, A., Horwitz, A.F., Lauffenburger, D.A.. Physical and biochemical regulation of integrin release during rear detachment of migrating cells. J. Cell Sci., 111 (1998), 929–940. Google ScholarPubMed
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 (1997), No. 6616, 537–540. CrossRefGoogle Scholar
Pankov, R., Yamada, K.M.. Fibronectin at a glance. J. Cell Sci., 115 (2002), No. 20, 3861–3863. CrossRefGoogle ScholarPubMed
Paszek, M.J., Boettiger, D., Weaver, V.M., Hammer, D.A.. Integrin clustering is driven by mechanical resistance from the glycocalyx and the substrate. PLoS Comput. Biol., 5 (2009), No. 12, e1000604. CrossRefGoogle Scholar
Pollard, T.D., Mooseker, M.S.. Direct measurement of actin polymerization rate constants by electron microscopy of actin filaments nucleated by isolated microvillus cores. J. Cell Biol., 88 (1981), No. 3, 654–659. CrossRefGoogle ScholarPubMed
Regen, C.M., Horwitz, A.F.. Dynamics of β1 integrin-mediated adhesive contacts in motile fibroblasts. J. Cell Biol., 119 (1992), No. 5, 1347–1359. CrossRefGoogle Scholar
Roy, S., Bingle, L., Marshall, J.F., Bass, R., Ellis, V., Speight, P.M., Whawell, S.A.. The role of alpha 9 beta 1 integrin in modulating epithelial cell behaviour. J. Oral Pathol., 40 (2011), No. 10, 755–761. CrossRefGoogle Scholar
Schmidt, H., Jirstrand, M.. Systems Biology Toolbox for MATLAB : a computational platform for research in systems biology. Bioinformatics, 22 (2006), No. 4, 514–515. CrossRefGoogle ScholarPubMed
Sechler, J.L., Takada, Y., Schwarzbauer, J.E.. Altered rate of fibronectin matrix assembly by deletion of the first type III repeats. J. Cell Biol., 134 (1996), No. 2, 573–583. CrossRefGoogle Scholar
Spassov, D.S., Wong, C.H., Sergina, N., Ahuja, D., Fried, M., Sheppard, D., Moasser, M.M.. Phosphorylation of trask by src kinases inhibits integrin clustering and functions in exclusion with focal adhesion signaling. Mol. Cell. Biol., 31 (2011), No. 4, 766–782. CrossRefGoogle ScholarPubMed
Takada, Y., Ye, X., Simon, S.. The integrins. Genome Biol., 8 (2007), No. 5, 215. CrossRefGoogle ScholarPubMed
Tamkun, J.W., Hynes, R.O.. Plasma fibronectin is synthesized and secreted by hepatocytes. J. Biol. Chem., 258 (1983), No. 7, 4641–4647. Google ScholarPubMed
Waldeck-Weiermair, M., Zoratti, C., Osibow, K., Balenga, N., Goessnitzer, E., Waldhoer, M., Malli, R., Graier, W.F.. Integrin clustering enables anandamide-induced Ca2+ signaling in endothelial cells via GPR55 by protection against CB1-receptor-triggered repression. J. Cell Sci., 121 (2008), 1704–1717. CrossRefGoogle ScholarPubMed
Webb, D.J., Parsons, J.T., Horwitz, A.R.. Adhesion assembly, disassembly and turnover in migrating cells - over and over and over again. Nat. Cell Biol., 4 (2002), No. 4, E97–E100. CrossRefGoogle Scholar
B. Wehrle-Haller. Analysis of integrin dynamics by fluorescence recovery after photobleaching. Adhesion Protein Protocols. Springer, 2007.
Wehrle-Haller, B., Imhof, B.A.. Actin, microtubules and focal adhesion dynamics during cell migration. Int. J. Biochem. Cell Biol., 35 (2003), No. 1, 39–50. CrossRefGoogle ScholarPubMed
Welf, E.S., Ogunnaike, B.A., Naik, U.P.. Quantitative statistical description of integrin clusters in adherent cells. IET Sys. Biol., 3 (2009), No. 5, 307–316. CrossRefGoogle ScholarPubMed
Wierzbicka-Patynowski, I., Schwarzbauer, J.. The ins and outs of fibronectin matrix assembly. J. Cell Sci., 116 (2003), No. 16, 3269–3276. CrossRefGoogle ScholarPubMed
Wiseman, P.W., Brown, C.M., Webb, D.J., Hebert, B., Johnson, N.L., Squier, J.A., Ellisman, M.H., Horwitz, A.F.. Spatial mapping of integrin interactions and dynamics during cell migration by image correlation microscopy. J. Cell Sci., 117 (2004), No. 23, 5521–5534. CrossRefGoogle ScholarPubMed
Yu, T., Wu, X., Gupta, K.B., Kucik, D.F.. Affinity, lateral mobility, and clustering contribute independently to β2-integrin-mediated adhesion. Am. J. Physiol. Cell Physiol., 299 (2010), No. 2, C399–C410. CrossRefGoogle Scholar
Zhang, F., Michaelson, J.E., Moshiach, S., Sachs, N., Zhao, W., Sun, Y., Sonnenberg, A., Lahti, J.M., Huang, H., Zhang, X.A.. Tetraspanin CD151 maintains vascular stability by balancing the forces of cell adhesion and cytoskeletal tension. Blood, 118 (2011), No. 15, 4274–4284. CrossRefGoogle ScholarPubMed