Cells, cancer, and rare events: homeostatic metastability in stochastic non-linear dynamics models of skin cell proliferation

TL;DR

This paper extends a skin cell proliferation model to include homeostasis as a fixed point, exploring how metastability and stochastic fluctuations can lead to cancer, providing insights into lung cancer epidemiology in ex-smokers.

Contribution

It introduces a novel extension of a cell proliferation model incorporating metastable homeostasis, linking stochastic dynamics to cancer onset.

Findings

Homeostatic fixed point can become metastable, allowing rare escape events.

Large stochastic fluctuations can trigger unlimited cell proliferation.

Model offers explanation for lung cancer epidemiology in ex-smokers.

Abstract

A recently proposed single progenitor cell model for skin cell proliferation [Clayton et al., Nature v446, 185 (2007)] is extended to incorporate homeostasis as a fixed point of the dynamics. Unlimited cell proliferation in such a model can be viewed as a paradigm for the onset of cancer. A novel way in which this can arise is if the homeostatic fixed point becomes metastable, so that the cell populations can escape from the homeostatic basin of attraction by a large but rare stochastic fluctuation. Such an event can be viewed as the final step in a multi-stage model of carcinogenesis. This offers a possible explanation for the peculiar epidemiology of lung cancer in ex-smokers.