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Intracellular Modelling of Cell-Matrix Adhesion during CancerCell Invasion

Published online by Cambridge University Press:  25 January 2012

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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.

Type
Research Article
Copyright
© EDP Sciences, 2012

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