CNSC-08. A STUDY ON THE ROLE OF PLATELET-DERIVED GROWTH FACTOR RECEPTOR A GENE REGULATION IN SUBVENTRICULAR ZONE CELLS RELATED TO GLIOBLASTOMA DEVELOPMENT

Abstract Glioblastoma (GBM) is an aggressive brain tumor known for frequent recurrence and treatment resistance. Recent studies suggest that neural stem cells (NSCs) in the subventricular zone (SVZ) may act as cells-of-origin for IDH-wildtype GBM. Platelet-derived growth factor receptor alpha (PDGFRα) is frequently overexpressed in GBM and is implicated in NSC proliferation, survival, and invasion. We hypothesize that PDGFRα plays a critical role in the growth and invasiveness of origin cells harboring driver mutations, thereby contributing to GBM malignancy. To test this, we compared PDGFRα expression among IDH1-wildtype GBM tumors, cortex, and ventricle tissues using RNA sequencing, and evaluated the effects of PDGFRα modulation on cell viability, ATP production, stemness, and invasiveness. Protein expression changes were assessed via Western blotting, and in vivo efficacy was validated using orthotopic mouse models. RNA sequencing revealed that PDGFRα expression was highest in tumor cells. While knockout (KO) of PDGFRα in normal SVZ cells produced no notable changes, its deletion in origin and tumor cells led to consistent reductions in cell viability, invasiveness, and stemness. In orthotopic models, mice implanted with PDGFRα KO cells exhibited longer survival and smaller tumors compared to controls. Conversely, overexpression of PDGFRα in origin cells enhanced invasiveness, consistent with in vitro KO findings. These results confirm the pivotal role of PDGFRα in driving malignancy-related phenotypes in origin cells and support its relevance in GBM pathogenesis. Our study suggests that PDGFRα is not only a marker of aggressiveness but may also represent a therapeutic target for disrupting the early progression of IDH-wildtype GBM. Targeting PDGFRα in SVZ-origin GBM may offer a novel avenue for limiting tumor growth and improving clinical outcomes.