STEM-05. GLIOBLASTOMA NEUROSPHERES DISPLAY STEMNESS CHARACTERISTICS AND UPREGULATION OF THE VEGF-A PATHWAY

Abstract INTRODUCTION Glioma stem cells (GSC) constitute a subpopulation of tumor with stem-cell like properties and are believed to enhance glioblastoma’s ability grow confer resistance against chemoradiotherapy. It has been shown that non-adherent three-dimensional (3D) growth conditions facilitate neurosphere formation enable isolation GSCs in vitro. This can serve as an invaluable tool better understand the role glioblastoma pathogenesis. OBJECTIVE We aimed evaluate differentially expressed genes versus adherent using primary cell lines; identify alterations various signaling pathways paramount their maintenance. Furthermore, we targeted EMP2-HIF1α axis, proposed regulator VEGF expression, determine its effects on viability. METHODS Three lines were generated cultured under or conditions. Sequencing was performed Illumina HiSeq3000 system, gene counts normalized by TMM. A pair-wise statistical analysis over 20,000 between two p-value < 0.05 considered statistically significant. RESULTS After 72 hours 3D conditions, show increase stem-like properties, measured via upregulation SOX2 nestin. RNA sequencing demonstrated significant expression following transcripts compared those grown plates: VEGF-A, EGFR, PDGFR-A, FGFR3, TGFB2. Treatment anti-EMP2 monoclonal antibodies significantly reduced cellular proliferation. CONCLUSION Our results demonstrate neurospheres upregulate factor survival suggesting inherently different genetic landscape differentiated GSCs. Future studies will investigate mechanisms responsible for these genes; ultimately design more effective therapeutic agents.