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

First Author  Jiménez B Year  2000
Journal  Nat Med Volume  6
Issue  1 Pages  41-8
PubMed ID  10613822 Mgi Jnum  J:119249
Mgi Id  MGI:3701582 Doi  10.1038/71517
Citation  Jimenez B, et al. (2000) Signals leading to apoptosis-dependent inhibition of neovascularization by thrombospondin-1. Nat Med 6(1):41-8
abstractText  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.
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