The Journal of Experimental Medicine
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Published online 15 May 2000.
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© The Rockefeller University Press, 0022-1007/2000/5/1789/ $5.00
The Journal of Experimental Medicine, Volume 191, Number 10, May 15, 2000 1789-1798

Original Article

Thrombospondin-1 Is Downregulated by Anoxia and Suppresses Tumorigenicity of Human Glioblastoma Cells

Mirna Tenana, Giulia Fulcia, Michele Albertonia, Annie-Claire Diserensa, Marie-France Hamoua, Michèle El Atifi-Borelc, Jean-Jacques Feiged, Michael S. Peppere, and Erwin G. Van Meira,b

a Laboratory of Tumor Biology and Genetics, Neurosurgery Department, University Hospital (CHUV), 1011 Lausanne, Switzerland
b Laboratory of Molecular Neuro-Oncology, Neurosurgery Department and Winship Cancer Center, Emory University, Atlanta, Georgia 30322
c Laboratory of Biochemistry A, University Hospital (CHRG), F-38043 Grenoble, France
d Institut National de la Santé et de la Recherche Médicale (INSERM) Unit 244, Department of Molecular and Structural Biology, Commissariat à l'Énergie Atomique (CEA), F-38054 Grenoble, France
e Department of Morphology, University of Geneva Medical Center, 1211 Geneva 4, Switzerland
Laboratory of Molecular Neuro-Oncology, Winship Cancer Institute, Emory University, 1365-B Clifton Rd. NE, Rm. B5103, Atlanta, GA 30322.404-778-5240404-778-5227

evanmei{at}emory.edu

Angiogenesis, the sprouting of new capillaries from preexisting blood vessels, results from a disruption of the balance between stimulatory and inhibitory factors. Here, we show that 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.

Key Words: tumor • angiogenesis • glioma • p53 • GD-AIF

Abbreviations used in this paper: aFGF, acidic fibroblast growth factor; bFGF, basic fibroblast growth factor; GD-AIF, glioma-derived angiogenesis inhibitory factor; TIMP-1, tissue inhibitor of metalloproteinase 1; TSP-1, thrombospondin-1; VEGF, vascular endothelial growth factor; wt, wild-type.

© 2000 The Rockefeller University Press


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