N. Yamaguchi et al., Endostatin inhibits VEGF-induced endothelial cell migration and tumor growth independently of zinc binding, EMBO J, 18(16), 1999, pp. 4414-4423
Endostatin, produced as recombinant protein in human 293-EBNA cells, inhibi
ts the migration of human umbilical vein endothelial cells (HUVECs) in resp
onse to vascular endothelial growth factor (VEGF) in a dose-dependent manne
r and prevents the subcutaneous growth of human renal cell carcinomas in nu
de 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 af
fected by mutations which eliminate Zn or heparin binding and inhibition of
tumor growth does not depend on Zn binding. The results of the migration a
ssays suggest that endostatin causes a block at one or more steps in VEGF-i
nduced migration, while VEGF in turn can cause a block of the inhibition by
endostatin of VEGF-induced migration of HUVECs.