Glioma stem cell proliferation and tumor growth are promoted by nitric oxide synthase-2.

Published

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 2011

Published In

Volume / Issue

  • 146 / 1

Start / End Page

  • 53 - 66

PubMed ID

  • 21729780

Pubmed Central ID

  • 21729780

Electronic International Standard Serial Number (EISSN)

  • 1097-4172

International Standard Serial Number (ISSN)

  • 0092-8674

Digital Object Identifier (DOI)

  • 10.1016/j.cell.2011.06.006

Language

  • eng