Thrombospondin-1 is downregulated by anoxia and suppresses tumorigenicity of human glioblastoma cells.
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.
Tenan
M
M
Laboratory of Tumor Biology and Genetics, Neurosurgery Department, University Hospital (CHUV), 1011 Lausanne, Switzerland.
Fulci
G
G
Albertoni
M
M
Diserens
A C
AC
Hamou
M F
MF
El Atifi-Borel
M
M
Feige
J J
JJ
Pepper
M S
MS
Van Meir
E G
EG
D000818:Animals; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D015536:Down-Regulation; D016158:Genes, p53; D005909:Glioblastoma / Q000098:blood supply / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D000860:Hypoxia / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D019700:Thrombospondin 1 / Q000096:biosynthesis / Q000235:genetics*; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D017931:DNA Primers; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D019700:Thrombospondin 1