Inhibitory effects of a bacteria-derived sulfated polysaccharide against basic fibroblast growth factor-induced endothelial cell growth and chemotaxis.
The effects of sulfated polysaccharides on the growth and chemotaxis of endothelial cells promoted by basic fibroblast growth factor (bFGF), a heparin-binding growth factor, and epidermal growth factor (EGF), a non-heparin-binding growth factor, were examined. The binding abilities of these two growth factors to D-gluco-D-galactan sulfate (DS-4152) were the same as to heparin. DS-4152 inhibited the growth and chemotaxis of the cells stimulated by bFGF, and prevented the binding of bFGF to the cells at both its low and high affinity binding sites: the former and the latter are heparin-like molecules and receptor proteins for bFGF, respectively. However, DS-4152 affected neither the binding of EGF to endothelial cells nor the proliferation and chemotaxis of the cells stimulated by the factor. Heparin also inhibited the binding of bFGF to low affinity binding sites to the same degree as DS-4152, but had little effect on the binding of bFGF to high affinity sites and no effects on bFGF-induced endothelial cell growth. Chondroitin sulfate A prevented neither the binding of bFGF to both sites of the cells nor bFGF-induced cell proliferation. We thus concluded that the inhibitory effects of DS-4152 against the growth and chemotaxis of endothelial cells induced by bFGF might be due to the prevention of bFGF binding to its receptor proteins resulting from the binding of DS-4152 to bFGF.
Nakayama
Y
Y
Exploratory Research Laboratories I, Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan.
Iwahana
M
M
Sakamoto
N
N
Tanaka
N G
NG
Osada
Y
Y
D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002633:Chemotaxis / Q000187:drug effects*; D004730:Endothelium, Vascular / Q000166:cytology*; D004815:Epidermal Growth Factor / Q000378:metabolism / Q000502:physiology; D016222:Fibroblast Growth Factor 2 / Q000037:antagonists & inhibitors* / Q000502:physiology; D006801:Humans; D007700:Kinetics; D011135:Polysaccharides, Bacterial / Q000378:metabolism / Q000494:pharmacology*
D011135:Polysaccharides, Bacterial; D016222:Fibroblast Growth Factor 2; C079061:tecogalan; D004815:Epidermal Growth Factor