On the impact of chemo-mechanically induced phenotypic transitions in gliomas

ABSTRACT Tumor microenvironment is a critical player in glioma progression and novel therapies for its targeting have been recently proposed. In particular, stress-alleviation strategies act on the tumor by reducing its stiffness, decreasing solid stresses and improving blood perfusion. However, these microenvironmental changes trigger chemo-mechanically induced cellular phenotypic transitions whose impact on therapy outcomes is not completely understood. In this work, we perform experiments to analyze the effects of mechanical compression on migration and proliferation of two glioma cell lines. From these experiments, we derive a mathematical model of glioma progression focusing on cellular phenotypic plasticity. The model reveals a trade-off between tumor infiltration and cellular content as a consequence of stress-alleviation approaches. We discuss how these findings can improve the current understanding of glioma/microenvironment interactions, and suggest strategies to improve therapeutic outcomes.