eNOS expression is elevated in human glioblastomas and correlated with greater tumor development and aggressive character. We investigated the possible selleck chem Vincristine part of nitric oxide (NO) action while in the perivascular niche (PVN) employing a genetic engineered mouse model of PDGF-induced gliomas. eNOS expression is highly elevated in tumor vascular endothelium adjacent to perivascular glioma cells expressing Nestin, Notch, and also the NO receptor, Dipeptidyl peptidase-4 (DPP4) sGC. Additionally, the NO/cGMP/PKG pathway drives Notch signaling in PIDGF-induced gliomas in vitro, and induces the side population phenotype in key glioma cell cultures. NO also increases neurosphere forming capacity of PDGF-driven glioma primary cultures, and enhances their tumorigenic capacity in vivo. Reduction of NO action in these tumors suppresses Notch signaling in vivo and prolongs survival of mice. This mechanism is conserved in human PDGFR amplified gliomas. The NO/cGMP/PKG pathway's promotion of stem cell-like character inside the tumor PVN may perhaps identify therapeutic targets for this subset of gliomas.