CNSC-16. BIDIRECTIONAL SIGNALING BETWEEN GLIOBLASTOMA AND NEURAL PROGENITORS EXPLORED WITH CELL-SPECIFIC PROTEOMICS RESULTS IN INCREASED TUMOR MALIGNANCY AND ALTERED NEUROGENESIS IN THE SUBVENTRICULAR ZONE

Abstract Glioblastoma (GBM) is the most common and aggressive primary neoplasm of central nervous system. The location GBM contributes significantly to patient outcomes, where tumors contacting lateral ventricles (LVs) have increased expression stem cell genes, incidence distal recurrence, decreased overall survival. While reasons for these findings are not fully understood, we hypothesize they arise due interactions with subventricular zone (SVZ), largest neurogenic niche in mammals. We examined bidirectional signals between cells neural progenitor (NPCs) vitro vivo using a combination patient-derived intraoperative samples, preclinical animal models, methionine tRNA synthetase L274G (MetRS*) nascent proteomic labeling system, which allows cell-specific proteomics analysis from complex systems. In co-culture NPCs, increase their viability, proliferation, migration, malignancy-promoting proteins, including migratory proteins such as TAGLN, PALLD, STAT1. vivo, tumor proximity SVZ results stemness markers, survival, altered tumor-specific proteome. then reciprocal effect on NPC biology. proliferation induced neuronal maturation NPCs. To determine changes created transgenic mouse line Nestin-CreERT2; STOPflox R26-MetRS L274G, upon tamoxifen administration Nestin+ NPCs express GFP MetRS*. Our indicate that LV-proximal induces Eml1, VGLUT1, EAAT2, an pro-migratory factors Lamc1 conclusion, there neurogenesis malignancy GBM. signaling identified our studies will result identification novel therapeutic targets