When a collective outcome triggers a rare individual event: a mode of metastatic process in a cell population

Abstract : A model of early metastatic process is based on the role of the protein PAI-1, which at high enough extracellular concentration promotes the transition of cancer cells to a state prone to migration. This transition is described at the single cell level as a bi-stable switch associated with a subcritical bifurcation. In a multilevel reaction-diffusion scenario, the microenvironment of the tumor is modified by the proliferating cell population so as to push the concentration of PAI-1 above the bifurcation threshold. The formulation in terms of partial differential equations fails to capture spatio-temporal heterogeneity. Cellular-automata and agent-based simulations of cell populations support the hypothesis that a randomly localized accumulation of PAI-1 can arise and trigger the escape of a few isolated cells. Far away from the primary tumor, these cells experience a reverse transition back to a proliferative state and could generate a secondary tumor. The proposed role of PAI-1 in controlling this metastatic cycle is candidate to explain its role in the progression of cancer.
Type de document :
Pré-publication, Document de travail
2009
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  • HAL Id : hal-00407546, version 2

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Michel Malo, Amandine Cartier-Michaud, Elizabeth Fabre-Guillevin, Guillaume Hutzler, Franck Delaplace, et al.. When a collective outcome triggers a rare individual event: a mode of metastatic process in a cell population. 2009. 〈hal-00407546v2〉

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