Quantitative effects of intercellular signals on computer-simulated tumor patterns.

The behavior of tumor cells within a particular in vivo microenvironment is considered to be regulated by intercellular signals. Previous studies of computer simulations of tumor growth demonstrated a qualitative effect of autocrine and paracrine signaling factors on the resulting morphologic patterns. We investigated the quantitative effect of these intercellular signals when the evolving patterns were evaluated by a set of pattern analysis procedures, yielding 18 quantitative morphologic features. The results show that both autocrine and paracrine factors regulating either tumor cell proliferation, motility or death influenced at least 10 of the 18 features significantly (linear regression analysis; n = 50 for each experiment; P = < .01). Furthermore, multivariate analysis of 600 simulated patterns also demonstrated highly significant relationships between intercellular signals and quantitative features of the evolving pattern (P = < .001). The study showed that various pattern measurement features indicate a direct influence of intercellular signals on tumor patterns in computer simulations.