Signals leading to apoptosis-dependent inhibition of neovascularization by thrombospondin-1
Signals leading to apoptosis-dependent inhibition of neovascularization by thrombospondin-1
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DOI：
10.1038/71517
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发表时间：
2000-01-01
期刊：
影响因子：
82.9
通讯作者：
Bouck, N
中科院分区：
文献类型：
--
作者：
Jiménez, B;Volpert, OV;Bouck, N
血小板反应蛋白-1（TSP-1）是一种天然存在的血管生成抑制剂，可限制正常组织中的血管密度并抑制肿瘤生长。在这里，我们表明，在体外和体内的血管生成的抑制和诱导细胞凋亡的血小板反应蛋白-1都需要依次激活的CD 36，p59（fyn），半胱天冬酶-3样蛋白酶和p38丝裂原活化蛋白激酶。我们还检测到血小板反应蛋白-1治疗的小鼠肿瘤边缘原位内皮细胞凋亡增加。这些结果表明，血小板反应蛋白-1，并可能其他广谱天然抑制剂的血管生成，在体内通过诱导受体介导的活化微血管内皮细胞凋亡。
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, p59(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.