Computational analysis of the influence of the microenvironment on carcinogenesis.

The tumour microenvironment is known to play an important role in determining the sequence of acquired phenotypic traits that characterise cancer evolution. A more precise understanding of this role could have a major influence in the understanding of cancer growth and development, and potentially in the optimisation of innovative anti-cancer treatments delivery. However, to lead such an analysis in the basis of traditional biological experiments and observations is almost utopian given the complexity of the underlying biological processes and the typical time scales involved. In this context, computer models constitute a complementary exploratory tool. In this paper we introduce a two-dimensional cellular automaton that models key cancer cell capabilities. The model has been especially designed to mimic the behaviour of a cancer colony growing in vitro and to analyse the effect of different environmental conditions on the sequence of acquisition of phenotypic traits. Our results indicate that microenvironmental factors such as the local concentration of oxygen or nutrients and cell overcrowding may determine the expansion of the tumour colony. The results also show that tumour cells evolve and that their phenotypes adapt to the microenvironment so that environmental stress determines the dominance of particular phenotypical traits.