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Modeling Steps from a Begnin Tumor to an Invasive Cancer: Examples of Instrinsically Multiscale Problems

By Dirk Drasdo, Nick Jagiella, Ignacio Ramis-Conde, Irene Vignon-Clementel and William Weens

Abstract

The step from benign tumors to invasive cancer is characterized by neovascularization, detachment of cells from the main tumor and eventually invasion of cells into the surrounding tissue and blood vessels leading to distant metastases. We will for each of these steps show how experimental observations can be explained by the interplay of processes on the molecular and the cellular scale within a framework using individual-based models. The representation of the cell in the models permits us to represent physical, particularly biomechanical, constraints.We first study how a neoformation of blood vessels can affect the development of tumor size and shape if the nutrients transported in the vessels control the growth rate of the individual cells. Cell detachment is often triggered by a misfunctioning of the beta-catenin-degrading apparatus in the cytosol.We demonstrate how an elevated beta-catenin concentration in one cell can trigger a cascade of other cells stepwise detaching as well, which then can migrate freely into the surrounding tissue. Before the cells can form distant metastasis, they need to invade blood vessels.We show how the competition between N-CAM and VE-cadherin bonds can facilitate invasion of a cancer cell into a blood vessel if the involved pathways have defects

Topics: [ PHYS.MECA.BIOM ] Physics [physics]/Mechanics [physics]/Biomechanics [physics.med-ph], [ SPI.MECA.BIOM ] Engineering Sciences [physics]/Mechanics [physics.med-ph]/Biomechanics [physics.med-ph], [ SDV.BC.IC ] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], [ INFO.INFO-MO ] Computer Science [cs]/Modeling and Simulation
Publisher: Taylor & Francis
Year: 2010
OAI identifier: oai:HAL:inria-00542749v1
Provided by: Hal-Diderot
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