Endostatin: An endogenous inhibitor of angiogenesis and tumor growth
Endostatin: An endogenous inhibitor of angiogenesis and tumor growth
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DOI：
10.1016/s0092-8674(00)81848-6
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发表时间：
1997-01-24
期刊：
影响因子：
64.5
通讯作者：
Folkman, J
中科院分区：
文献类型：
--
作者：
OReilly, MS;Boehm, T;Folkman, J
我们以前确定了血管生成抑制剂angiostatin。使用类似的策略，我们已经确定内皮抑素，血管生成抑制剂产生的血管内皮瘤。内皮抑素是胶原XVIII的20 kDa C-末端片段。内皮抑素特异性抑制内皮细胞增殖，并有效抑制血管生成和肿瘤生长。通过一种新的缓释方法，E.大肠杆菌来源的内皮抑制素以非重折叠的悬浮液形式给药。原发性肿瘤消退为休眠的显微镜病变。免疫组化显示，阻断血管生成伴随着高增殖平衡的肿瘤细胞凋亡。没有毒性。与血管抑制素数据一起，这些发现验证了用于鉴定内源性血管生成抑制剂的策略，提出了作为血管生成抑制剂的蛋白质片段的主题，并证明了休眠疗法。
We previously identified the angiogenesis inhibitor angiostatin. Using a similar strategy, we have identified endostatin, an angiogenesis inhibitor produced by hemangioendothelioma. Endostatin is a 20 kDa C-terminal fragment of collagen XVIII. Endostatin specifically inhibits endothelial proliferation and potently inhibits angiogenesis and tumor growth. By a novel method of sustained release, E. coli-derived endostatin was administered as a nonrefolded suspension. Primary tumors were regressed to dormant microscopic lesions. Immunohistochemistry revealed blocked angiogenesis accompanied by high proliferation balanced by apoptosis in tumor cells. There was no toxicity. Together with angiostatin data, these findings validate a strategy for identifying endogenous angiogenesis inhibitors, suggest a theme of fragments of proteins as angiogenesis inhibitors, and demonstrate dormancy therapy.