Signals leading to apoptosis-dependent inhibition of neovascularization by thrombospondin-1. Nat Med 2000 Jan;6(1):41-8
Date
12/29/1999Pubmed ID
10613822DOI
10.1038/71517Scopus ID
2-s2.0-0342445431 (requires institutional sign-in at Scopus site) 900 CitationsAbstract
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, p59fyn, 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.
Author List
Jiménez B, Volpert OV, Crawford SE, Febbraio M, Silverstein RL, Bouck NAuthor
Roy L. Silverstein MD Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AngiostatinsAnimals
Apoptosis
CD36 Antigens
Caspases
Endothelium, Vascular
Fibroblast Growth Factor 2
Humans
Lung Neoplasms
Melanoma, Experimental
Mice
Mice, Knockout
Microcirculation
Mitogen-Activated Protein Kinases
Neovascularization, Pathologic
Neovascularization, Physiologic
Peptide Fragments
Plasminogen
Protein-Tyrosine Kinases
Proto-Oncogene Proteins
Proto-Oncogene Proteins c-fyn
Signal Transduction
Thrombospondin 1
p38 Mitogen-Activated Protein Kinases
