Glioma stem cell proliferation and tumor growth are promoted by nitric oxide synthase-2.
Glioma stem cell proliferation and tumor growth are promoted by nitric oxide synthase-2.
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胶质瘤干细胞增殖和肿瘤生长由一氧化氮合酶2促进。
DOI：
10.1016/j.cell.2011.06.006
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发表时间：
2011-07-08
期刊：
影响因子：
64.5
通讯作者：
Rich JN
中科院分区：
文献类型：
--
作者：
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
恶性胶质瘤是侵袭性脑肿瘤，治疗选择有限，治疗的改进需要对这种疾病有更深入的分子理解。与其他癌症一样，最近的研究已经确定了恶性胶质瘤中高度致瘤性的亚群，通常称为癌症干细胞。在这里，我们证明了胶质瘤干细胞（GSC）通过一氧化氮合酶-2（NOS 2）表达升高产生一氧化氮。GSC依赖于NOS 2活性来生长和致瘤，将它们与非GSC和正常神经祖细胞区分开来。基因表达谱鉴定了许多NOS 2调节基因，包括细胞周期抑制剂细胞分裂自身抗原1（CDA 1）。此外，高NOS 2表达与人神经胶质瘤患者的存活率降低相关，并且NOS 2抑制减缓了鼠颅内模型中神经胶质瘤的生长。这些数据提供了对GSC与其致瘤性较低的对应物在机制上如何不同的见解，并表明NOS 2抑制可能是治疗这种毁灭性疾病的有效方法。
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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影响因子：
5.2
作者：
Bar, Eli E.;Chaudhry, Aneeka;Eberharta, Charles G.
通讯作者：
Eberharta, Charles G.
DOI：
10.1073/pnas.95.18.10378
发表时间：
1998-09-01
影响因子：
11.1
作者：
Gardner, PR;Gardner, AM;Salzman, AL
通讯作者：
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影响因子：
8.8
作者：
Avontuur, JAM;Nolthenius, RPT;Bruining, HA
通讯作者：
Bruining, HA
影响因子：
11.2
作者：
Galli, R;Binda, E;Vescovi, A
通讯作者：
Vescovi, A
影响因子：
4.4
作者：
Bakshi, A;Nag, TC;Sarkar, C
通讯作者：
Sarkar, C