Syrokou A, Tzanakakis G, Tsegenidis T, Hjerpe A, Karamanos N K
Department of Chemistry, University of Patras, Greece.
Cell Prolif. 1999 Apr-Jun;32(2-3):85-99. doi: 10.1046/j.1365-2184.1999.32230085.x.
Proteoglycans interact with other effective macromolecules regulating a variety of cellular events via their glycosaminoglycan (GAG) chains. The effects of all known glycosaminoglycans (GAGs) produced by normal cells and tissues on the proliferation of two human malignant mesothelioma cell lines, one with fibroblast-like morphology and the other with epithelial differentiation - both able to produce hyaluronan (HA), galactosaminoglycans (GalAGs) and heparan sulphate (HS) containing proteoglycans - have been studied. Cell proliferation was assessed by measuring [3H]thymidine incorporation and cell number. GalAGs, i.e. chondroitin sulphates (CSs) and dermatan sulphate (DS), strongly stimulate the proliferation of fibroblast-like cells in a dose-dependent manner (170-250% at 100 microg/ml), independently of their sulphation pattern. In epithelial cells, however, only DS stimulates cell proliferation. The effects of CSs on proliferation of epithelial cells are not depended on their sulphation pattern. Thus, CSs either with -[GlcA-GalNAc-(-6-O-SO(3)-)]- or -[GlcA-GalNAc-(-4-O-SO(3)-]- as the commonest unit, had no significant effect. L-Iduronic acid (IdoA)-rich heparin and fast-moving HS (fm-HS), a HS fraction with a heparin-like structure, had significant antiproliferative effects on mesothelioma cells of both types (30-70% at 1.0 microg/ml and 85-90% at 100 microg/ml, respectively). GlcA-rich HS, however, had no significant effects. HA inhibits only the proliferation of fibroblast-like cells by 25% at 50 and 100 microg/ml. Keratan sulphate suppresses cell proliferation (10-30%) in both cell lines. In the view of these findings, a structure-function relationship of GAGs on cell proliferation of the two human malignant mesothelioma cell lines is discussed. Other factors, such as chain conformation and geometry, as well as interactions of growth factors with GAGs, possibly involved in the regulation of cell proliferation, are also discussed.
蛋白聚糖通过其糖胺聚糖（GAG）链与其他有效的大分子相互作用，从而调节多种细胞活动。研究了正常细胞和组织产生的所有已知糖胺聚糖（GAGs）对两种人类恶性间皮瘤细胞系增殖的影响，这两种细胞系一种具有成纤维细胞样形态，另一种具有上皮分化特征，二者均能产生透明质酸（HA）、半乳糖胺聚糖（GalAGs）和含硫酸乙酰肝素（HS）的蛋白聚糖。通过测量[3H]胸腺嘧啶核苷掺入量和细胞数量来评估细胞增殖。GalAGs，即硫酸软骨素（CSs）和硫酸皮肤素（DS），以剂量依赖方式强烈刺激成纤维细胞样细胞的增殖（100μg/ml时为170 - 250%），且与它们的硫酸化模式无关。然而，在上皮细胞中，只有DS能刺激细胞增殖。CSs对上皮细胞增殖的影响不依赖于其硫酸化模式。因此，以-[GlcA - GalNAc - (-6 - O - SO(3)-)]- 或 -[GlcA - GalNAc - (-4 - O - SO(3)-]- 作为最常见单元的CSs均无显著影响。富含L -艾杜糖醛酸（IdoA）的肝素和快速移动的HS（fm - HS，一种具有类肝素结构的HS组分）对两种类型的间皮瘤细胞均有显著的抗增殖作用（分别在1.0μg/ml时为30 - 70%，在100μg/ml时为85 - 90%）。然而，富含GlcA的HS没有显著影响。HA仅在50和100μg/ml时抑制成纤维细胞样细胞的增殖25%。硫酸角质素在两种细胞系中均抑制细胞增殖（10 - 30%）。基于这些发现，讨论了GAGs对两种人类恶性间皮瘤细胞系细胞增殖的结构 - 功能关系。还讨论了其他可能参与细胞增殖调节的因素,如链构象和几何形状，以及生长因子与GAGs的相互作用。
