Thrombospondin-1 is downregulated by anoxia and suppresses tumorigenicity of human glioblastoma cells

被引:85
作者
Tenan, M
Fulci, G
Albertoni, M
Diserens, AC
Hamou, MF
El Atifi-Borel, M
Feige, JJ
Pepper, MS
Van Meir, EG
机构
[1] Emory Univ, Winship Canc Inst, Dept Neurosurg, Mol Neurooncol Lab, Atlanta, GA 30322 USA
[2] CHU Vaudois, Dept Neurosurg, Lab Tumor Biol & Genet, CH-1011 Lausanne, Switzerland
[3] Emory Univ, Winship Canc Ctr, Atlanta, GA 30322 USA
[4] CHRG, Lab Biochem A, F-38043 Grenoble, France
[5] CEA, Dept Biol Mol & Struct, INSERM, U244, F-38054 Grenoble, France
[6] Univ Geneva, Med Ctr, Dept Morphol, CH-1211 Geneva 4, Switzerland
关键词
tumor; angiogenesis; glioma; p53; GD-AIF;
D O I
10.1084/jem.191.10.1789
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Angiogenesis, the sprouting of new capillaries from preexisting blood vessels, results hom a disruption of the balance between stimulatory and inhibitory factors. Here, we show chat anoxia reduces expression of thrombospondin-1 (TSP-1), a natural inhibitor of angiogenesis, in glioblastoma cells. This suggests that reduced oxygen tension can promote angiogenesis not only by stimulating the production of inducers, such as vascular endothelial growth factor, but also by reducing the production of inhibitors. This downregulation may significantly contribute to glioblastoma development, since we show that an increase in TSP-1 expression is sufficient to strongly suppress glioblastoma cell tumorigenicity in vivo.
引用
收藏
页码:1789 / 1797
页数:9
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