Fig. 3.

Adhesion receptor regulation scenarios. At the beginning of simulations the tumour cell population of interest can either be homogeneous, i.e. γ=0 (HOM), or heterogeneous, i.e. γ>0 (HET), regarding intrinsic cell-cell adhesivity. Furthermore, the regulation of single cell adhesion receptor concentration can either be independent, i.e. α=0 (CONTROL ⁻), or controlled by the environment, i.e α>0 (CONTROL ⁺), the latter via a weight that increases adhesion receptor expression with increasing local cell density. With this weight, we model a cellular adhesion phenotype under environmental control. Combination of these possibilities gives four adhesion receptor regulation scenarios: Scenario I corresponds to a healthy tissue which we assume to be homogeneous and in which adhesion receptor concentration is under environmental control (γ=0 and α>0). Scenario II corresponds to adhesion heterogeneity caused by differential adhesion receptor expression in the cells, for example due to mutations which are expected to be found in malignant cells (γ>0 and α>0). Scenario III corresponds to a tissue in which cells are still homogeneous but the environmental control is impaired (γ=0 and α=0). This is also expected in malignant cells. Scenario IV is a combination of both heterogeneity and impaired environmental control (γ>0 and α=0)