Inhibitory effect of full-length human endostatin on in vitro angiogenesis

Endostatin, a C-terminal product of collagen XVIII, is a very powerful angi ogenesis inhibitor. In vivo experiments in mice indicate that endostatin dr amatically reduces tumor mass without causing the onset of any resistance t o the treatment. Recently, a 12-aa shorter human endostatin has been purifi ed from plasma, but is ineffective in in vitro angiogenesis assays. Here we report that the full-length human recombinant endostatin has a potent inhi bitory activity in in vitro angiogenesis assays. Two powerful angiogenic fa ctors were used to stimulate endothelial cells: FGF-2 and VEGF-165. Endosta tin prevented cell growth both in the basal condition and after stimulation with FGF-2 or VEGF-165. Migration of microvascular endothelial cells towar d FGF-2 or VEGF-165 was impaired, both when cells mere pretreated with the inhibitor and when endostatin was added together with the growth factors. F urthermore, experiments of inhibition of proliferation performed on nonmicr oendothelial cells showed that endostatin was ineffective. This study indic ates that human endostatin is a potent angiogenesis inhibitor and suggests its use in human anticancer therapy. (C) 1999 Academic Press.