title: Cells, cancer, and rare events: homeostatic metastability in stochastic nonlinear dynamical models of skin cell proliferation.
abstract: A recently proposed model for skin cell proliferation [E. Clayton, Nature (London) 446, 185 (2007)] is extended to incorporate mitotic autoregulation, and hence homeostasis as a fixed point of the dynamics. Unlimited cell proliferation in such a model can be viewed as a model for carcinogenesis. One way in which this can arise is homeostatic metastability, in which the cell populations 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 multistage model of carcinogenesis. Homeostatic metastability offers a possible explanation for the peculiar epidemiology of lung cancer in ex-smokers.
authors.affiliation: Unilever R&D Port Sunlight, Bebington, Wirral CH63 3JW, United Kingdom.
authors.forename: Patrick B
authors.initials: PB
authors.lastname: Warren
mesh_terms: D049109:Cell Proliferation; D006706:Homeostasis; D008175:Lung Neoplasms / Q000473:pathology; D008954:Models, Biological; D009362:Neoplasm Metastasis / Q000473:pathology; D017711:Nonlinear Dynamics; D015398:Signal Transduction; D012867:Skin / Q000166:cytology* / Q000378:metabolism / Q000473:pathology*; D012878:Skin Neoplasms / Q000378:metabolism / Q000473:pathology*; D013269:Stochastic Processes