When a Collective Outcome Triggers a Rare Individual Event: A Mode of Metastatic Process in a Cell Population

Michel Malo, Amandine Cartier-Michaud, Elisabeth Fabre-Guillevin, Guillaume Hutzler, Franck Delaplace, Georgia Barlovatz-Meimon and Annick Lesne

Mathematical Population Studies, 2010, vol. 17, issue 3, 136-165

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 micro-environment 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 suggested role of PAI-1 in controlling this metastatic cycle is candidate to explain its role in the progression of cancer.

Keywords: agent-based simulation; cell population; metastastic escape; multilevel model; multistability; reaction-diffusion (search for similar items in EconPapers)
Date: 2010
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DOI: 10.1080/08898480.2010.490996

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