Endostatin inhibits VEGF-induced endothelial cell migration and tumor growth independently of zinc binding

被引：398

作者：

Yamaguchi, N

Anand-Apte, B

Lee, M

Sasaki, T

Fukai, N

Shapiro, R

Que, I

Lowik, C

Timpl, R

Olsen, BR ^{[1
]}

机构：

[1] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA

[2] Cleveland Clin Fdn, Dept Cell Biol NC10, Cleveland, OH 44195 USA

[3] Max Planck Inst Biochem, D-82152 Martinsried, Germany

[4] Harvard Univ, Sch Med, Ctr Biochem & Biophys Sci & Med, Boston, MA 02115 USA

[5] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA

[6] Leiden Univ, Ctr Med, NL-2300 RC Leiden, Netherlands

来源：

EMBO JOURNAL | 1999年 / 18卷 / 16期

关键词：

angiogenesis; endostatin; heparin binding; tumor growth; zinc binding;

D O I：

10.1093/emboj/18.16.4414

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：4414 / 4423

页数：10

共 20 条

[1] Zinc-binding of endostatin is essential for its antiangiogenic activity [J].