Abstract:
: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.
journal_name
Celljournal_title
Cellauthors
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 JNdoi
10.1016/j.cell.2011.06.006subject
Has Abstractpub_date
2011-07-08 00:00:00pages
53-66issue
1eissn
0092-8674issn
1097-4172pii
S0092-8674(11)00648-9journal_volume
146pub_type
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