Effects of glycosaminoglycans on proliferation of epithelial and fibroblast human malignant mesothelioma cells: a structure–function relationship

Abstract

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.

Xyloside-primed Chondroitin Sulfate/Dermatan Sulfate from Breast Carcinoma Cells with a Defined Disaccharide Composition Has Cytotoxic Effects in Vitro

“…For example, HS fragments generated after heparinase I treatment or heparinase III treatment of tumor cells have been shown to either promote or inhibit tumor growth in vivo, depending on their composition (25). Similarly, treatment of melanoma cells with chondroitinase AC or chondroitinase B has been reported to inhibit growth and migration in vitro (26), and other studies have showed inhibition as well as promotion of cell growth by HS and CS/DS (27)(28)(29). Here, we demonstrated that the CS/DS was responsible for the cytotoxic effect of the XylNapOHprimed GAGs from HCC70 cells, whereas the XylNapOHprimed HS did not have any effect on cell growth.…”

Isolation and Characterization of Chondroitin Sulfates from Sturgeon (<i>Acipenser sinensis</i>) and Their Effects on Growth of Fibroblasts

“…Therefore, fibroblasts adhesion and migration are essential to wound healing. 34) In this study, CS could stimulate fibroblasts to adhere, proliferate, and migrate into the wound space.…”

Diagnostic and prognostic significance of glypican 5 and glypican 6 gene expression levels in gastric adenocarcinoma

“…Glypicans are composed of a core protein molecule and ≥1 glycosaminoglycan chains that are covalently bound to specific sites on this core. HSPGs are structural components of tissue organization and have important biological functions in cellular proliferation, adhesion, migration and differentiation (7,8), all of which depend on interactions with extracellular and/or cytoplasmic ligands (9).…”