Abstract B34: PDGFR-ID4-Notch axis is a common signaling pathway activated in glioma stem cells and endothelial cells

Abstract

Abstract Glioma stem cells (GSCs), which reside within the perivascular niche (PVN) to maintain self-renewal capacity, are responsible for glioblastoma initiation, progression, and recurrence. However, the molecular mechanisms controlling GSCs and endothelial cells in the PVN are poorly understood. Here, we report that PDGF-driven activation of nitric oxide (NO) synthase increases NO-dependent ID4 expression, which promotes Jagged-Notch activity through miR-129 suppression in GSCs and endothelial cells. ID4 also increases PDGF-PDGFR signaling in a direct or miR-129-dependent manner, which drives the PDGFR-NO-ID4 signaling in GSCs and endothelial cells. This signaling circuit promotes tumor progression along with increased GSC self-renewal and growth of tumor vasculature in the PVN, which is dramatically suppressed by Notch inhibitor. ID4 levels correlate positively with NOS2, Hes1, and Hey1 and negatively with miR-129 in primary GSCs. Thus, targeting the PDGFR-NO-ID4 signaling circuit and Notch activity in the PVN might serve as an efficacious therapeutic modality for glioblastoma. Citation Format: Hye-Min Jeon, Hyunggee Kim. PDGFR-ID4-Notch axis is a common signaling pathway activated in glioma stem cells and endothelial cells. [abstract]. In: Proceedings of the AACR Special Conference: Advances in Brain Cancer Research; May 27-30, 2015; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2015;75(23 Suppl):Abstract nr B34.