Angiogenesis is a complex process consisting of the proliferation, migration and differentiation of endothelial cells, and it is essential for the progression of malignant solid tumors. In this report, we examine the effects of disintegrins (e.g. rhodostomin and accutin) and glycoprotein-lb-binding proteins (e.g. agkistin) on each step in angiogenesis using in vitro and in vivo models. Rhodostomin (but not agkistin) inhibited the viability of human umbilical vein endothelial cells (HUVECs) and capillary tube formation of HUVECs. Rhodostomin also inhibited HUVEC migration and invasion evoked by basic fibroblast growth factor (bFGF). In in vivo studies, rhodostomin inhibited bFGF-, but not vascular-endothelial-growth-factor (VEGF)- associated angiogenesis in chick chorioallantoic membrane model, blocked both bFGF and B16F10 melanoma cell-induced neovascularization, and suppressed the growth of subcutaneously inoculated B16F10 solid tumor, leading to a prolonged survival of the C57BL/6 mice treated with rhodostomin. The antiangiogenic effects of rhodostomin on bFGF-treated HUVECs may be mainly related to the blockade of the interaction of endothelial alpha(v)beta(3) and extracellular matrix.
Copyright 2002 S. Karger AG, Basel