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Pré-Publication, Document De Travail Année : 2009

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

Résumé

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.
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Dates et versions

hal-00407546 , version 1 (26-07-2009)
hal-00407546 , version 2 (28-07-2009)

Identifiants

  • HAL Id : hal-00407546 , version 2

Citer

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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