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

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  • MICHEL MALO
  • AMANDINE CARTIER-MICHAUD
  • ELISABETH FABRE-GUILLEVIN
  • GUILLAUME HUTZLER
  • FRANCK DELAPLACE
  • GEORGIA BARLOVATZ-MEIMON
  • ANNICK LESNE

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.

Suggested Citation

  • Michel Malo & Amandine Cartier-Michaud & Elisabeth Fabre-Guillevin & Guillaume Hutzler & Franck Delaplace & Georgia Barlovatz-Meimon & Annick Lesne, 2010. "When a Collective Outcome Triggers a Rare Individual Event: A Mode of Metastatic Process in a Cell Population," Mathematical Population Studies, Taylor & Francis Journals, vol. 17(3), pages 136-165.
    • Handle: RePEc:taf:mpopst:v:17:y:2010:i:3:p:136-165
    DOI: 10.1080/08898480.2010.490996
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    References listed on IDEAS

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    1. Moritz Gerstung & Niko Beerenwinkel, 2010. "Waiting Time Models of Cancer Progression," Mathematical Population Studies, Taylor & Francis Journals, vol. 17(3), pages 115-135.
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