RT Journal Article
SR Electronic
T1 On the impact of chemo-mechanically induced phenotypic transitions in gliomas
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 476150
DO 10.1101/476150
A1 Pietro Mascheroni
A1 Juan Carlos Lopez Alfonso
A1 Maria Kalli
A1 Triantafyllos Stylianopoulos
A1 Michael Meyer-Hermann
A1 Haralampos Hatzikirou
YR 2018
UL http://biorxiv.org/content/early/2018/12/06/476150.abstract
AB 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.