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

• Type of Material: Article
• Authors: Mirna Tenan, University Hospital (CHUV), Switzerland; Giulia Fulci, University Hospital (CHUV), Switzerland; Michele Albertoni, University Hospital (CHUV), Switzerland; Annie-Claire Diserens, University Hospital (CHUV), Switzerland; Marie-France Hamou, University Hospital (CHUV), Switzerland; Michele El Atifi-Borel, University Hospital (CHRG), France; Jean-Jacques Feige, Commissariat à l'Énergie Atomique (CEA), France; Michael S. Pepper, University of Geneva Medical Center, Switzerland; Erwin Van Meir, Emory University
• Language: English
• Date: 2000-05-15
• Publisher: Rockefeller University Press
• Publication Version: Final Published Version
• Copyright Statement: © 2000 The Rockefeller University Press
• License: Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International
• Final Published Version (URL): http://jem.rupress.org/content/191/10/1789.full?sid=1355be82-547d-4fb7-8b84-662392baf695
• Title of Journal or Parent Work: Journal of Experimental Medicine
• ISSN: 0022-1007
• Volume: 191
• Issue: 10
• Start Page: 1789
• End Page: 1798
• Grant/Funding Information: This work was supported by the Italian Association for Cancer Research (to M. Tenan), Swiss National Science Foundation grants 31-49194.96 and 4037-044729, Swiss Cancer Research Foundation grant KFS172-9-1995, National Institutes of Health grant CA86335, and the San Salvatore Foundation (all to E.G. Van Meir), and by MBNA America Bank, N.A.
• Keywords: GD-AIF; p53; angiogenesis; tumor; glioma
• Research Categories: Health Sciences, Oncology

Abstract

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.