The Role of Microenvironment in Regulation of Cell Infiltration in Glioblastoma

Glioblastoma multiforme (GBM) is one of the deadliest human cancers and is characterized by fast growth and aggressive invasion. GBM also communicates with microglia and macrophages which are recruited by tumor cells to facilitate growth and invasion. In this study we investigate the biochemical and cell-mechanical interactions between the glioma cells and the microenvironment including resident glial cells and M1/M2 microglia that enhance tumor invasion. We develop various types of mathematical models that involve reaction-diffusion equations or multi-scale hybrid models for the important components in this mutual interaction. In particular, we investigate the dynamics of intracellular signaling including miR-451 and AMPK, biochemical interaction of a glioma with M1/M2 microglia via CSF-1-EGF-TGF-β signaling, and glioma cell infiltration through the narrow intercellular space via the regulation of myosin II. We show that these models can replicate the key features of the experimental findings and make novel predictions to guide future experiments aimed at the development of new anti-invasive strategies.