Growth of mixed cancer cell population - in silico the size matters.

Cancer heterogeneity is still underexplored and difficult to investigate. The whole network of factors engaged in tumor growth makes clinical cases, as well as the in vivo and in vitro experiments, of limited use in terms of understanding cancer heterogeneity. Our idea was to start from scratch and focus on the simplest distinctive feature in a heterogeneous tumor, namely the cell size. To exclude any other factors, we created a rudimentary cellular automata model of mixed cancer culture with two lines of different cell sizes. We tested the model with various sets of parameters to explore how the cell size affects cancer co-culture growth. It turned out that the cell size plays a crucial role in in silico heterogeneous tumor growth. The dominance of bigger cells decreases the number of cells in the overall mixed cancer population. In contrast, the small cells increase the total number of cells, even without a parallel enlargement of the macroscopic tumor size. Predominance of the smaller cells is particularly visible under overcrowded conditions. Although our model was primarily designed for verification of experimental hypothesis and as a mean for better understanding of the cancer heterogeneity itself, it also has some practical value. Our findings can affect today's practice of estimating tumor growth based on its macroscopic size and may propose a new approach to interpreting histological data. After modifications, the model may serve to test other factors affecting growth of mixed populations of cancer cells differing in size.