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Data Supplement from Crosstalk between Glioma-Initiating Cells and Endothelial Cells Drives Tumor Progression

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posted on 2023-03-30, 22:30 authored by Hye-Min Jeon, Sung-Hak Kim, Xun Jin, Jong Bae Park, Se Hoon Kim, Kaushal Joshi, Ichiro Nakano, Hyunggee Kim

Supplementary Figure S7. PDGF-NOS-ID4-miR-129 axis-relevant gene expression in tumor tissues derived from patients with GBM.

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ARTICLE ABSTRACT

Glioma-initiating cells (GIC), which reside within the perivascular microenvironment to maintain self-renewal capacity, are responsible for glioblastoma initiation, progression, and recurrence. However, the molecular mechanisms controlling crosstalk between GICs and endothelial cells are poorly understood. Here, we report that, in both GICs and endothelial cells, platelet-derived growth factor (PDGF)–driven activation of nitric oxide (NO) synthase increases NO-dependent inhibitor of differentiation 4 (ID4) expression, which in turn promotes JAGGED1–NOTCH activity through suppression of miR129 that specifically represses JAGGED1 suppression. This signaling axis promotes tumor progression along with increased GIC self-renewal and growth of tumor vasculature in the xenograft tumors, which is dramatically suppressed by NOTCH inhibitor. ID4 levels correlate positively with NOS2 (NO synthase-2), HES1, and HEY1 and negatively with miR129 in primary GICs. Thus, targeting the PDGF–NOS–ID4–miR129 axis and NOTCH activity in the perivascular microenvironment might serve as an efficacious therapeutic modality for glioblastoma. Cancer Res; 74(16); 4482–92. ©2014 AACR.

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