A TUMOR SUPPRESSOR-DEPENDENT INHIBITOR OF ANGIOGENESIS IS IMMUNOLOGICALLY AND FUNCTIONALLY INDISTINGUISHABLE FROM A FRAGMENT OF THROMBOSPONDIN
A TUMOR SUPPRESSOR-DEPENDENT INHIBITOR OF ANGIOGENESIS IS IMMUNOLOGICALLY AND FUNCTIONALLY INDISTINGUISHABLE FROM A FRAGMENT OF THROMBOSPONDIN
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DOI：
10.1073/pnas.87.17.6624
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发表时间：
1990-09-01
影响因子：
11.1
通讯作者：
BOUCK, NP
中科院分区：
文献类型：
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作者：
GOOD, DJ;POLVERINI, PJ;BOUCK, NP
仓鼠细胞中由肿瘤抑制基因控制的分泌型血管生成抑制剂已被发现与血小板和基质蛋白血小板反应蛋白的片段相似。这两种蛋白在生物化学上相似，在免疫学上具有交叉反应性，在两种功能检测中可以相互替代。人血小板反应蛋白抑制体内新血管形成和体外内皮细胞迁移，仓鼠蛋白gp140也是如此。与人血小板反应蛋白一样，gp 140使平滑肌细胞对表皮生长因子的刺激敏感。血小板反应蛋白基因定位于人类15号染色体上。这些结果表明，粘附糖蛋白血小板反应蛋白的功能，这可能是重要的正常生理下调新血管形成。此外，他们提出了这样一种可能性，即血小板反应蛋白可能是肿瘤抑制基因抑制肿瘤生长的靶分子之一。
A secreted inhibitor of angiogenesis that is controlled by a tumor suppressor gene in hamster cells has been found to be similar to a fragment of the platelet and matrix protein thrombospondin. The two proteins were biochemically similar and immunologically crossreactive and could substitute for one another in two functional assay. Human thrombospondin inhibited neovascularization in vivo and endothelial cell migration in vitro, as does the hamster protein, gp140. gp140 sensitized smooth muscle cells to stimulation by epidermal growth factor, as does human thrombospondin. The thrombospondin gene has been localized on human chromosome 15. These results demonstrate a function for the uniquitous adhesive glycoprotein thrombospondin that is likely to be important in the normal physiological down-regulation of neovascularization. In addition, they raise the possibility that thrombospondin may be one of a number of target molecules through which a tumor suppressor gene could act to restrain tumor growth.