Differential Endothelial Migration and Proliferation to Basic Fibroblast Growth Factor and Vascular Endothelial Growth Factor

Abstract

Neovascularization is a feature of a variety of pathological processes. We compared the characteristics of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) on migration and proliferation of human umbilical vein endothelium (HUVEC). Both VEGF and bFGF induced endothelial cell migration at similar concentrations (1/2 max. VEGF = approximately 1.0 ng/ml, bFGF = approximately 5.0 ng/ml). However, VEGF-stimulated migration was two-fold greater than bFGF at 1 and 10 ng/ml (p < 0.05). In contrast, bFGF induced proliferation four-fold more effectively than VEGF (1/2 max. 1 ng/ml and 1.4 ng/ml respectively). Checkerboard migration assays for bFGF showed a predominantly chemokinetic pattern, whereas VEGF was predominantly chemotactic. VEGF and bFGF were not synergistic in monolayer proliferation and migration assays. Three angiogenesis inhibitors, alpha-interferon, TNP-470, and platelet factor-4, inhibited VEGF and bFGF induced cell migration. These results indicate that VEGF and bFGF are chemoattractants that stimulate endothelial migration by different mechanisms and that both can be inhibited by known angiogenesis inhibitors.

Lymphangiogenesis by blind‐ended vessel sprouting is concurrent with hemangiogenesis by vascular splitting

“…Precise concentration gradients of VEGF-A support chemotactic cell migration and are required for correct blood vascular development in vivo (Carmeliet et al, 1996;Ferrara et al, 1996;Yoshida et al, 1996;Ozawa et al, 2004). Exogenous VEGF 165 stimulated the dilation and hyperfusion of blood vessels during early vasculogenesis throughout the primordial quail vascular plexus (Drake and Little, 1995).…”

Anti-tumor angiogenesis therapy using soluble receptors: enhanced inhibition of tumor growth when soluble fibroblast growth factor receptor-1 is used with soluble vascular endothelial growth factor receptor

“…[37 ]); 38,39 (f) in the quail chorioallantoic membrane, FGF -2 selectively stimulates the angiogenesis of smaller arteries, whereas VEGF dilates and increases the permeability of larger arteries; 40 (g) FGF -2 gene -disrupted mice are morphologically normal, 41,42 whereas VEGF -gene knockout mice die in utero with major angiogenic anomalies; 43 (h ) in human umbilical endothelial cells, FGF -2 is more potent at inducing cell proliferation than VEGF, but VEGF stimulates migration more effectively than FGF -2. 44 All these lend weight to the idea that multiple angiogenic factors, especially VEGFs and FGFs, cooperate to induce efficient tumor angiogenesis, and provide a further molecular basis supporting the potential usefulness of the combined application of sVEGFR and sFGFR1.…”

Differential expression of angiogenic cytokines by cell lines and primary cultures of human prostate cancer

“…u-PA mRNA expression in the parental sublines and Figure 3 Basic ®broblast growth factor has been shown to have important angiogenic effects in cancer. 4,8,13,22,28,33 bFGF stimulates endothelial cell proliferation and u-PA expression. 14 This facilitates matrix proteolysis for endothelial cell migration and neovascularization.…”