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Glioblastoma (GBM) is a dismal disease and despite optimal treatment, long-term survival remains uncommon. Molecular classification revealed three distinct GBM subgroups and has helped to shine light on the tumor’s inter/intratumoral heterogeneity. Interestingly, recent evidence shows plasticity between these subtypes in which the proneural (PN) glioma stem-like cells undergo transition into the more aggressive mesenchymal (MES) subtype leading to therapeutic resistance. Extracellular vesicles (EVs) are considered a heterogeneous group of membrane-limited vesicles secreted by nearly every cell. In the context of GBM, these biological nanoparticles act as multifunctional signaling complexes and play an important role in intercellular communication allowing cancer cells to exchange information with each other, the tumor microenvironment, and distant cells. We show that MES cells derived EVs modulate PN cells to increase migratory potential, stemness, invasiveness, aggressiveness, and therapeutic resistance by inducing mesenchymal transition through NF-KB/STAT3 signaling. Furthermore, we shine light on the role of EVs derived from irradiated GBM cells and their potential impact on microglia and resulting treatment resistance.

STEM-15. SMALL BUT FIERCE: THE ROLE OF EXTRACELLULAR VESICLES IN MESENCHYMAL TRANSITION AND THERAPEUTIC RESISTANCE IN GLIOBLASTOMA