Bagavandoss P, Wilks J W
Cancer Research, Upjohn Laboratories, Kalamazoo, MI 49001.
Biochem Biophys Res Commun. 1990 Jul 31;170(2):867-72. doi: 10.1016/0006-291x(90)92171-u.
Angiogenesis is a multi-step event involving endothelial cell migration, attachment, and proliferation. A thrombospondin (TSP)-like protein has recently been described as a naturally-occurring inhibitor of angiogenesis. We now report that human platelet TSP inhibits the in vitro proliferation of endothelial cells from the rabbit corpus luteum, bovine adrenal cortex and pulmonary artery, and human umbilical vein. The antiproliferative effect of TSP was neutralized by monoclonal antibodies against TSP. The growth arrest seen with TSP was specific for endothelial cells since TSP actually stimulated the growth of vascular smooth muscle cells and human foreskin fibroblasts. These results imply that the angiogenesis-inhibiting effect of TSP is mediated through an inhibition of endothelial cell proliferation. Elucidation of the mechanism of action of TSP on endothelial cell proliferation may lead to potential therapeutic approaches for the control of neovascular diseases.
血管生成是一个涉及内皮细胞迁移、黏附和增殖的多步骤过程。最近，一种血小板反应蛋白（TSP）样蛋白被描述为一种天然存在的血管生成抑制剂。我们现在报告，人血小板TSP可抑制来自兔黄体、牛肾上腺皮质和肺动脉以及人脐静脉的内皮细胞的体外增殖。TSP的抗增殖作用可被抗TSP单克隆抗体中和。TSP引起的生长停滞对内皮细胞具有特异性，因为TSP实际上刺激了血管平滑肌细胞和人包皮成纤维细胞的生长。这些结果表明，TSP的血管生成抑制作用是通过抑制内皮细胞增殖介导的。阐明TSP对内皮细胞增殖的作用机制可能会带来控制新生血管疾病的潜在治疗方法。
