Glioma stem cell proliferation and tumor growth are promoted by nitric oxide synthase-2.
Journal Article (Journal Article)
Malignant gliomas are aggressive brain tumors with limited therapeutic options, and improvements in treatment require a deeper molecular understanding of this disease. As in other cancers, recent studies have identified highly tumorigenic subpopulations within malignant gliomas, known generally as cancer stem cells. Here, we demonstrate that glioma stem cells (GSCs) produce nitric oxide via elevated nitric oxide synthase-2 (NOS2) expression. GSCs depend on NOS2 activity for growth and tumorigenicity, distinguishing them from non-GSCs and normal neural progenitors. Gene expression profiling identified many NOS2-regulated genes, including the cell-cycle inhibitor cell division autoantigen-1 (CDA1). Further, high NOS2 expression correlates with decreased survival in human glioma patients, and NOS2 inhibition slows glioma growth in a murine intracranial model. These data provide insight into how GSCs are mechanistically distinct from their less tumorigenic counterparts and suggest that NOS2 inhibition may be an efficacious approach to treating this devastating disease.
Full Text
Duke Authors
Cited Authors
- Eyler, CE; Wu, Q; Yan, K; MacSwords, JM; Chandler-Militello, D; Misuraca, KL; Lathia, JD; Forrester, MT; Lee, J; Stamler, JS; Goldman, SA; Bredel, M; McLendon, RE; Sloan, AE; Hjelmeland, AB; Rich, JN
Published Date
- July 8, 2011
Published In
Volume / Issue
- 146 / 1
Start / End Page
- 53 - 66
PubMed ID
- 21729780
Pubmed Central ID
- PMC3144745
Electronic International Standard Serial Number (EISSN)
- 1097-4172
Digital Object Identifier (DOI)
- 10.1016/j.cell.2011.06.006
Language
- eng
Conference Location
- United States