Suppression of glioblastoma angiogenicity and tumorigenicity by inhibition of endogenous expression of vascular endothelial growth factor

Shi Yuan Cheng, H. J Su Huang, Motoo Nagane, Xiang Dong Ji, Degui Wang, Charles C Y Shih, Wadih Arap, Chun Ming Huang, Webster K. Cavenee*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

317 Scopus citations

Abstract

The development of new capillary networks from the normal microvasculature of the host appears to be required for growth of solid tumors. Tumor cells influence this process by producing both inhibitors and positive effectors of angiogenesis. Among the latter, the vascular endothelial growth factor (VEGF) has assumed prime candidacy as a major positive physiological effector. Here, we have directly tested this hypothesis in the brain tumor, glioblastoma multiforme, one of the most highly vascularized human cancers. We introduced an antisense VEGF expression construct into glioblastoma cells and found that (i) VEGF mRNA and protein levels were markedly reduced, (ii) the modified cells did not secrete sufficient factors so as to be chemoattractive for primary human microvascular endothelial cells, (iii) the modified cells were not able to sustain tumor growth in immunodeficient animals, and (iv) the density of in vivo blood vessel formation was reduced in direct relation to the reduction of VEGF secretion and tumor formation. Moreover, revertant cells that recovered the ability to secrete VEGF regained each of these tumorigenic properties. These results suggest that VEGF plays a major angiogenic role in glioblastoma.

Original languageEnglish (US)
Pages (from-to)8502-8507
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume93
Issue number16
DOIs
StatePublished - Aug 6 1996

Keywords

  • antisense
  • human brain tumor
  • tumor angiogenesis

ASJC Scopus subject areas

  • General

Fingerprint

Dive into the research topics of 'Suppression of glioblastoma angiogenicity and tumorigenicity by inhibition of endogenous expression of vascular endothelial growth factor'. Together they form a unique fingerprint.

Cite this