Glioblastoma invasion relies on actomyosin contractility and metalloproteinase activity

Glioblastoma multiforme (GBM) is one of the most aggressive and invasive types of brain tumors with a 5-year survival rate of less than 20%. Due to its highly invasive phenotype, GBM cells tend to invade the surrounding normal brain tissue, making it challenging to fully resect the tumor and resulting in a relapse of the disease even after surgery. Hence, it is crucial to improve our mechanistic understanding of GBM invasion phenotype, in the hope of inhibiting the disease progression. Here, we used patient-derived GBM neurospheres as a model to study GBM invasion. When these neurospheres were cultured in Matrigel, the GBM cells spontaneously invaded the surrounding microenvironment. We first characterized the invasion rate through live imaging and the forces exerted by cells as they invade the Matrigel using traction force microscopy (TFM) analysis. We observed a significant increase in cellular contractility as the cells invaded the surrounding Matrigel, prompting us to investigate the role of myosin in the cell invasion. To test this, the GBM neurospheres were treated with a myosin inhibitor, Blebbistatin. Myosin inhibition led to reduced GBM invasion and contractility. Furthermore, we investigated the role of metalloproteinases (MMPs) and showed that GBM invasion relies on MMP activity in the absence of myosin. Together, this data shows the interplay between myosin and MMPs in GBM invasion.