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.
