Glioblastoma exosomes influence glial cell hyaluronic acid deposition to promote invasiveness

A deeper understanding of the mechanisms invoked by glioblastoma (GBM) to infiltrate the brain is needed to develop approaches to contain the disease and reduce recurrence. Here we report that GBM cells which have acquired a p53 mutation (p53273H) with established pro-invasive gain-of-function release exosomes/extracellular vesicles (EVs) containing a sialomucin, podocalyxin (PODXL), which encourages other brain cells, such as astrocytes to deposit extracellular matrix (ECM) with increased levels of hyaluronic acid (HA). This HA-rich ECM, in turn, promotes invasiveness of the GBM cells. Consistently, CRISPR-mediated deletion of PODXL opposes infiltration of GBM in vivo. This study offers a mechanistic basis for the particularly poor prognosis of GBM which are driven by the p53273H mutant, and how these tumours influence the wider brain ECM microenvironment through which glioma cells invade.