Imamura T, Mitsui Y
Cell Science and Technology Division, Agency of Industrial Science and Technology, Ibaraki, Japan.
Exp Cell Res. 1987 Sep;172(1):92-100. doi: 10.1016/0014-4827(87)90096-6.
The effects of glycosaminoglycans (GAGs), especially heparan sulfate, on human and porcine vascular endothelial cell growth in the presence of 10% fetal bovine serum (FBS) or so-called heparin-binding growth factors, acidic FGF (aFGF) or basic FGF (bFGF), were investigated in a series of studies in order to clarify their role in cell proliferation. The promotion of normal cell growth by aFGF was suppressed by heparan sulfate but enhanced by heparin, while growth promotion by bFGF was suppressed by both GAGs. Chondroitin sulfate and hyaluronic acid showed no significant suppression of promotion, even at much higher concentrations. The growth of spontaneously transformed cells was enhanced by heparan sulfate or heparin in the presence of 10% FBS or aFGF, while growth promotion in the presence of bFGF was suppressed by both GAGs. From these results, we concluded that heparan sulfate and heparin are not always functional analogs and that in some cases they exert opposite actions on the modulation of normal endothelial cell growth. The findings that heparan sulfate enhanced the growth of transformed cells but suppressed the growth of normal cells in the presence of 10% FBS or aFGF were consistent with those of our previous studies on human fibroblasts, confirming the occurrence of some common alterations in the signal transduction system or cell surface upon cellular transformation. The role of heparan sulfate in the modulation of endothelial cell proliferation in vivo is also discussed.
为了阐明糖胺聚糖（GAGs），尤其是硫酸乙酰肝素，在10%胎牛血清（FBS）或所谓的肝素结合生长因子、酸性成纤维细胞生长因子（aFGF）或碱性成纤维细胞生长因子（bFGF）存在的情况下对人和猪血管内皮细胞生长的影响，我们进行了一系列研究以明确它们在细胞增殖中的作用。硫酸乙酰肝素抑制了aFGF对正常细胞生长的促进作用，但肝素增强了这种作用，而bFGF介导的生长促进作用则受到两种GAGs的抑制。即使在浓度高得多的情况下，硫酸软骨素和透明质酸也未显示出对生长促进作用的显著抑制。在10% FBS或aFGF存在的情况下，硫酸乙酰肝素或肝素可增强自发转化细胞的生长，而在bFGF存在时，两种GAGs均抑制生长促进作用。根据这些结果，我们得出结论，硫酸乙酰肝素和肝素并不总是功能类似物，在某些情况下，它们对正常内皮细胞生长的调节作用相反。硫酸乙酰肝素在10% FBS或aFGF存在时增强转化细胞生长但抑制正常细胞生长的发现与我们之前对人成纤维细胞的研究结果一致，证实了细胞转化后信号转导系统或细胞表面发生了一些共同变化。本文还讨论了硫酸乙酰肝素在体内调节内皮细胞增殖中的作用。
