Identification of intrinsic in vitro cellular mechanisms for glioma invasion

Invasion of malignant glioma is a highly complex phenomenon involving molecular and cellular processes at various spatio-temporal scales, whose precise interplay is still not fully understood. In order to identify the intrinsic cellular mechanisms of glioma invasion, we study an in vitro culture of glioma cells. By means of a computational approach, based on a cellular automaton model, we compare simulation results to the experimental data and deduce cellular mechanisms from microscopic and macroscopic observables (experimental data). For the first time, it is shown that the migration/proliferation dichotomy plays a central role in the invasion of glioma cells. Interestingly, we conclude that a diverging invasive zone is a consequence of this dichotomy. Additionally, we observe that radial persistence of glioma cells in the vicinity of dense areas accelerates the invasion process. We argue that this persistence results from a cell-cell repulsion mechanism. If glioma cell behavior is regulated through a migration/proliferation dichotomy and a self-repellent mechanism, our simulations faithfully reproduce all the experimental observations.

► We model glioma growth and invasion by means of a lattice-gas cellular automaton model. ► We identify cellular mechanisms associated with invasion based on an in vitro invasion assay. ► The migration/proliferation dichotomy plays a central role in glioma invasion. ► Radial persistence of glioma cells can be explained by a cell–cell repulsion mechanism. ► Regulation of the phenotype switch by the local density promotes invasion.