Montebello: A Metapopulation Based Model of Carcinogenesis

Abstract

The dynamics of the lengthy process by which tumors arise from normal tissues is not well understood. We developed a stochastic cellular automaton model based on the ecological concept of metapopulations to explore the role of mutation, exogenous disturbance, and selection in the genesis of tumors. The operation of the model shows how disturbances (e.g. inflammation) acting on tissues can cause tumors by modifying the dynamics among metapopulations of cells. Simulations demonstrate that disturbance, without change in mutation rates, can drive tumor formation. Changes in the distribution of genetic alterations among metapopulations in the tissue can predict the emergence of a tumor, thus providing a measure of risk. Modifying the disturbance regimen can prevent the emergence of tumors. Thus, the model provides insights into how mutation rates and disturbance interact in the causation of cancer, and illustrate how measuring metapopulation distributions can provide surrogate end points for preventive intervention.