Differential endothelial migration and proliferation to basic fibroblast growth factor and vascular endothelial growth factor.
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.
Yoshida
A
A
Department of Surgery Children's Hospital Boston, Massachusetts 02115, USA.
Anand-Apte
B
B
Zetter
B R
BR
D002452:Cell Count; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D002633:Chemotaxis; D003510:Cyclohexanes; D016228:Endothelial Growth Factors / Q000494:pharmacology*; D004727:Endothelium / Q000378:metabolism*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology; D008222:Lymphokines / Q000494:pharmacology*; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D010978:Platelet Factor 4 / Q000494:pharmacology; D011994:Recombinant Proteins / Q000235:genetics / Q000494:pharmacology; D012717:Sesquiterpenes / Q000494:pharmacology; D014471:Umbilical Veins / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D003510:Cyclohexanes; D016228:Endothelial Growth Factors; D016898:Interferon-alpha; D008222:Lymphokines; D011994:Recombinant Proteins; D012717:Sesquiterpenes; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2; D010978:Platelet Factor 4; D000077609:O-(Chloroacetylcarbamoyl)fumagillol