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

Publication ,  Journal Article
Eyler, CE; Wu, Q; Yan, K; MacSwords, JM; Chandler-Militello, D; Misuraca, KL; Lathia, JD; Forrester, MT; Lee, J; Stamler, JS; Goldman, SA ...
Published in: Cell
July 8, 2011

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.

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Published In

Cell

DOI

EISSN

1097-4172

Publication Date

July 8, 2011

Volume

146

Issue

1

Start / End Page

53 / 66

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Nitric Oxide Synthase Type II
  • Nitric Oxide
  • Neural Stem Cells
  • Neoplastic Stem Cells
  • Mice, Transgenic
  • Mice
  • Humans
  • Glioma
  • Disease Models, Animal
 

Citation

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Eyler, C. E., Wu, Q., Yan, K., MacSwords, J. M., Chandler-Militello, D., Misuraca, K. L., … Rich, J. N. (2011). Glioma stem cell proliferation and tumor growth are promoted by nitric oxide synthase-2. Cell, 146(1), 53–66. https://doi.org/10.1016/j.cell.2011.06.006
Eyler, Christine E., Qiulian Wu, Kenneth Yan, Jennifer M. MacSwords, Devin Chandler-Militello, Katherine L. Misuraca, Justin D. Lathia, et al. “Glioma stem cell proliferation and tumor growth are promoted by nitric oxide synthase-2.Cell 146, no. 1 (July 8, 2011): 53–66. https://doi.org/10.1016/j.cell.2011.06.006.
Eyler CE, Wu Q, Yan K, MacSwords JM, Chandler-Militello D, Misuraca KL, et al. Glioma stem cell proliferation and tumor growth are promoted by nitric oxide synthase-2. Cell. 2011 Jul 8;146(1):53–66.
Eyler, Christine E., et al. “Glioma stem cell proliferation and tumor growth are promoted by nitric oxide synthase-2.Cell, vol. 146, no. 1, July 2011, pp. 53–66. Pubmed, doi:10.1016/j.cell.2011.06.006.
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. Glioma stem cell proliferation and tumor growth are promoted by nitric oxide synthase-2. Cell. 2011 Jul 8;146(1):53–66.
Journal cover image

Published In

Cell

DOI

EISSN

1097-4172

Publication Date

July 8, 2011

Volume

146

Issue

1

Start / End Page

53 / 66

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Nitric Oxide Synthase Type II
  • Nitric Oxide
  • Neural Stem Cells
  • Neoplastic Stem Cells
  • Mice, Transgenic
  • Mice
  • Humans
  • Glioma
  • Disease Models, Animal