(582f) Targeting Hyaluronan Interactions for Glioblastoma Stem Cell Therapy

Glioblastoma multiforme (GBM) patients have an abysmal median survival rate, greatly due to the drug-resistant glioblastoma stem cell (GSC) population. GSCs are known to remodel their microenvironment, but the precise role of extracellular matrix components hyaluronic acid (HA) and hyaluronidases (HAases) on the GSC population is still largely unknown. Our objective was to determine how HAase can sensitize GSCs to chemotherapy drugs by disrupting the HA-CD44 signaling. Here, we found that HA supplementation promoted the expression of GSC markers and CD44 in GBM cells cultured in serum-free media. Conversely, HAase addition inhibited GSC gene expression while promoting CD44 expression. Finally, HAase sensitized GBM cells to TMZ. We therefore propose a combined treatment of HAase and chemotherapy drugs by disrupting the stemness-promoting HA to target GSCs. This combination therapy shows promise even when temozolomide treatment alone causes resistance.