Signals leading to apoptosis-dependent inhibition of neovascularization by thrombospondin-1

Benilde Jiménez, Olga V. Volpert, Susan E. Crawford*, Maria Febbraio, Roy L. Silverstein, Noël Bouck

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

812 Scopus citations

Abstract

Thrombospondin-1 (TSP-1) is a naturally occurring inhibitor of angiogenesis that limits vessel density in normal tissues and curtails tumor growth. Here, we show that the inhibition of angiogenesis in vitro and in vivo and the induction of apoptosis by thrombospondin-1 all required the sequential activation of CD36, p57(fyn), caspase-3 like proteases and p38 mitogen-activated protein kinases. We also detected increased endothelial cell apoptosis in situ at the margins of tumors in mice treated with thrombospondin-1. These results indicate that thrombospondin-1, and possibly other broad-spectrum natural inhibitors of angiogenesis, act in vivo by inducing receptor-mediated apoptosis in activated microvascular endothelial cells.

Original languageEnglish (US)
Pages (from-to)41-48
Number of pages8
JournalNature Medicine
Volume6
Issue number1
DOIs
StatePublished - Jan 2000

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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