GLIOMA INTERACTION WITH THE NEUROGENIC NICHE THROUGH EXTRACELLULAR VESICLES

PROJECT SUMMARY/ABSTRACT Glioblastoma (GBM) is the most common, aggressive and proliferative primary brain tumor in adults despite current therapeutic strategies that combine surgery, radiation, and chemotherapy. The high invasive capacity of GBM makes total surgical resection virtually impossible, resulting in an extremely high recurrence rate. The

ability to form a new tumor resides in a subpopulation of cells within the GBM called brain tumor initiating cells (BTICs). BTICs are undifferentiated cells with self-renewing and pluripotential capacity, similar to neural stem cells (NSCs), but with the added ability of forming tumors in vivo. Our group and others have reported that

among primary GBMs, those that are located in close proximity to the lateral ventricles (LV) present multiple factors, including increased recurrence at distant locations, that negatively affect patients’ survival. Possible explanations may involve the proximity of these tumors to the cerebrospinal fluid (CSF) and neurogenic niche in

the subventricular zone (SVZ). We have previously reported that GBM tumors infiltrating the LV disrupt SVZ homeostasis, inducing signs of senescence in NPC and allowing CSF infiltration. The ensuing interaction with CSF heightens the proliferation and migration capacity of GBM-BTICs, fostering a more aggressive phenotype.

However, the mechanisms used by GBM cells to modify the SVZ niche and the LV wall are not understood. In our preliminary studies we have observed extracellular vesicles (EVs) play an important role in the intercellular communication between BTICs and NPCs. The proposal's primary objective is to explore the role of EVs in

mediating communication between GBM cells and the tumor microenvironment, specifically within the SVZ. Additionally, the research aims to evaluate EVs as potential biomarkers for monitoring brain tumor response to treatment and predicting recurrence.