Numerical Investigation of the Effect of Loss of Cellular Polarity on Cancer Invasiveness and Geometry

We have investigated the effect of loss of cell polarity at the individual cell level on the global pattern formation of squamous cell carcinoma. Simple models of cancer growth are able to reproduce qualitatively the sequence of observed abnormalities of metaplasia, dysplasia and carcinoma in situ and invasive carcinoma. The models are based on loss of cell polarity alone by cancerous cells, coupled to an otherwise normal growth rate and epithelial behavior. The models show that, as the probability of a wrong plane of cell division is increased, a transition from normal, well stratified epithelium, to an invasive, fractal, dendritic pattern is observed. This transition shows a sequence of morphologies in the following order as a function of loss of polarity: first an apparently normal but already diseased tissue, then metaplasic followed by a dysplasic tissue, and eventually carcinoma first in situ, then invasive. The model also suggests a killing mechanism of most severe cancer clones towards weaker ones.