CNSC-02. INVESTIGATING THE ROLE OF THE WNT SIGNALING TRANSDUCTION PATHWAY IN GLIOMA BLOOD-BRAIN-BARRIER INTEGRITY

Abstract The WNT signaling transduction pathway has been linked to cancer stem cell self-renewal, differentiation, and blood brain barrier (BBB) development. Previous studies have shown that inhibition increased BBB permeability, specifically in medulloblastoma. Glioblastoma, an aggressive malignant tumor with poor prognosis, also high expression variable permeability. We hypothesize activating glioblastoma cells (GSCs) will inhibit glioma progression, increase permeability within the microenvironment, enhance overall treatment responsiveness. transduced primary pediatric derived overexpressing vectors for inhibitors (DKK1 or WIF1). To characterize effects of DKK1 WIF1 overexpression, we evaluated migration patterns via RTCA xCelligence, cycle progression Annexin 5 assays, viability cell-titer glo. Brain endothelial integrity was CHIR99021, activator, GSC condition media immunoblotting junctional protein (Claudin-5, Claudin-3, Occludin, ZO-1, VE-Cadherin). Verification inhibitory GSCs performed using RNAseq, proteomics, immunoblotting. DKK1-GSCs demonstrated a statistically significant impairment migratory slope compared empty vector GSCs. Cell analysis revealed were arrested G0/1 phase while WIF1-GSCs S/G2M phase. CHIR99021 resulted secretion SFRP1 resultantly, there decrease expression. Overall, inhibitor exhibited unique cellular indirectly disrupted integrity. Future evaluate orthotopic transplant rodent models determine integrity, drug model survival, chemotherapeutic response. By enhancing our understanding GSCs, anticipate use future therapeutic targeting responsiveness improve prognosis.