Endostatin inhibits VEGF-induced endothelial cell migration and tumor growth independently of zinc binding
Endostatin inhibits VEGF-induced endothelial cell migration and tumor growth independently of zinc binding
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DOI：
10.1093/emboj/18.16.4414
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发表时间：
1999-08-16
期刊：
影响因子：
11.4
通讯作者：
Olsen, BR
中科院分区：
文献类型：
--
作者：
Yamaguchi, N;Anand-Apte, B;Olsen, BR
内皮抑素作为重组蛋白在人293-EBNA细胞中产生，以剂量依赖的方式抑制人脐静脉内皮细胞（HUVECs）对血管内皮生长因子（VEGF）的迁移，并在浓度和剂量比先前报道的浓度和剂量低1000至10万倍的情况下，阻止裸鼠体内人肾细胞癌的皮下生长。对迁移的抑制不受消除锌或肝素结合的突变的影响，肿瘤生长的抑制也不依赖于锌的结合。迁移实验结果表明，内皮抑素在VEGF诱导迁移的一个或多个步骤中引起阻滞，而VEGF反过来又可以引起内皮抑素对VEGF诱导的huvec迁移的抑制。
Endostatin, produced as recombinant protein in human 293-EBNA cells, inhibits the migration of human umbilical vein endothelial cells (HUVECs) in response to vascular endothelial growth factor (VEGF) in a dose-dependent manner and prevents the subcutaneous growth of human renal cell carcinomas in nude mice at concentrations and in doses that are from 1000- to 100 000-fold lower than those previously reported, The inhibition of migration is not affected by mutations which eliminate Zn or heparin binding and inhibition of tumor growth does not depend on Zn binding. The results of the migration assays suggest that endostatin causes a block at one or more steps in VEGF-induced migration, while VEGF in turn can cause a block of the inhibition by endostatin of VEGF-induced migration of HUVECs.