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

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          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, 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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          Author and article information

          Journal
          Nat Med
          Nature medicine
          Springer Science and Business Media LLC
          1078-8956
          1078-8956
          Jan 2000
          : 6
          : 1
          Affiliations
          [1 ] Department of Microbiology, Robert H. Lurie Comprehensive Cancer Center, Chicago, Illinois, 60611, USA.
          Article
          10.1038/71517
          10613822
          fa45ecc3-ea92-4ad0-a191-6f3ce1b0f81b
          History

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