Glioma Stem Cell Proliferation and Tumor Growth Are Promoted by Nitric Oxide Synthase-2 | Zendy

Christine E. Eyler | Zendy; Qiulian Wu | Zendy; Kenneth Yan | Zendy; Jennifer MacSwords | Zendy; Devin Chandler-Militello | Zendy; Katherine L. Misuraca | Zendy; Justin D. Lathia | Zendy; Michael T. Forrester | Zendy; Jeongwu Lee | Zendy; Jonathan S. Stamler | Zendy; Steven A. Goldman | Zendy; Markus Bredel | Zendy; Roger E. McLendon | Zendy; Andrew E. Sloan | Zendy; Anita B. Hjelmeland | Zendy; Jeremy N. Rich | Zendy

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Glioma Stem Cell Proliferation and Tumor Growth Are Promoted by Nitric Oxide Synthase-2

Author(s) -

Christine E. Eyler,

Qiulian Wu,

Kenneth Yan,

Jennifer MacSwords,

Devin Chandler-Militello,

Katherine L. Misuraca,

Justin D. Lathia,

Michael T. Forrester,

Jeongwu Lee,

Jonathan S. Stamler,

Steven A. Goldman,

Markus Bredel,

Roger E. McLendon,

Andrew E. Sloan,

Anita B. Hjelmeland,

Jeremy N. Rich

Publication year - 2011

Publication title -

cell

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 26.304

H-Index - 776

eISSN - 1097-4172

pISSN - 0092-8674

DOI - 10.1016/j.cell.2011.06.006

Subject(s) - biology , glioma , stem cell , cancer research , neural stem cell , cancer stem cell , nitric oxide synthase , progenitor cell , nitric oxide , cell cycle , cell growth , brain tumor , cell culture , cell , pathology , microbiology and biotechnology , genetics , endocrinology , medicine

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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