Perivascular nitric oxide activates notch signaling and promotes stem-like character in PDGF-induced glioma cells Journal Article

   

Authors:	Charles, N.; Ozawa, T.; Squatrito, M.; Bleau, A. M.; Brennan, C. W.; Hambardzumyan, D.; Holland, E. C.
Article Title:	Perivascular nitric oxide activates notch signaling and promotes stem-like character in PDGF-induced glioma cells
Abstract:	eNOS expression is elevated in human glioblastomas and correlated with increased tumor growth and aggressive character. We investigated the potential role of nitric oxide (NO) activity in the perivascular niche (PVN) using 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 the NO receptor, sGC. In addition, the NO/cGMP/PKG pathway drives Notch signaling in PDGF-induced gliomas in vitro, and induces the side population phenotype in primary glioma cell cultures. NO also increases neurosphere forming capacity of PDGF-driven glioma primary cultures, and enhances their tumorigenic capacity in vivo. Loss of NO activity 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 in the tumor PVN may identify therapeutic targets for this subset of gliomas. © 2010 Elsevier Inc. All rights reserved.
Keywords:	signal transduction; platelet derived growth factor; controlled study; nonhuman; drug targeting; glioma; mouse; phenotype; animals; mice; animal tissue; mus; cell line; animal experiment; animal model; notch receptor; in vivo study; in vitro study; tumor cell culture; mice, scid; tumor cells, cultured; carcinogenesis; stem cell; survival time; genetic engineering; vascular endothelium; neoplastic stem cells; glioma cell; receptors, notch; stemcell; platelet-derived growth factor; cellcycle; mice, inbred nod; tumor vascularization; nestin; receptors, platelet-derived growth factor; chickens; nitric oxide; cyclic gmp; cyclic gmp dependent protein kinase; endothelial nitric oxide synthase; cyclic gmp-dependent protein kinases; nitric oxide synthase type iii
Journal Title:	Cell Stem Cell
Volume:	6
Issue:	2
ISSN:	1934-5909
Publisher:	Cell Press
Date Published:	2010-02-01
Start Page:	141
End Page:	152
Language:	English
DOI:	10.1016/j.stem.2010.01.001
PUBMED:	20144787
PROVIDER:	scopus
PMCID:	PMC3818090
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-75349091751&partnerID=40&md5=6be39ca87d210fc713ef4544d182b883
Notes:	--- - "Cited By (since 1996): 17" - "Export Date: 20 April 2011" - "Source: Scopus"

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