The modulation of thrombospondin and other naturally occurring inhibitors of angiogenesis during tumor progression

Olga V. Volpert*, Veronica Stellmach, Noel Bouck

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

90 Scopus citations

Abstract

Fifteen different natural inhibitors of angiogenesis have now been identified that are produced by mammalian cells and are able to block in vivo neovascularization. The majority of these are able to inhibit endothelial cell activities in vitro and all those tested have demonstrated significant antitumor activity. Most normal cells produce inhibitors of neovascularization that must be downregulated before the cells can develop into angiogenic, malignant tumors. In several cases the production of inhibitors ceases when tumor suppressor genes are inactivated. In the BT549 human breast carcinoma cell line, the reintroduction of a wild type p53 tumor suppressor gene resulted in the stimulation of the secretion of an inhibitor of angiogenesis, thrombospondin-1, and as a result the cells lost their angiogenic phenotype and became able to suppress angiogenesis induced by the parental tumor line. These results provide a new example of tumor suppressor gene control of a natural inhibitor of angiogenesis and add support to the concept that thrombospondin loss may play an important role in the development of some human breast cancers.

Original languageEnglish (US)
Pages (from-to)119-126
Number of pages8
JournalBreast Cancer Research and Treatment
Volume36
Issue number2
DOIs
StatePublished - Jan 1 1995

Keywords

  • breast carcinoma cell lines
  • neovascularization
  • p53
  • thrombospondin
  • tumor suppressor genes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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