Altered content composition and structure of glycosaminoglycans and proteoglycans in gastric carcinoma

Abstract

Glycosaminoglycans (GAGs) in proteoglycan (PG) forms or as free GAGs are implicated in the growth and progression of malignant tumors. These macromolecules were investigated in human gastric carcinoma (HGC) and compared with those in human normal gastric mucosa (HNG). We report that HGC contained about 2-fold increased amounts of GAGs in comparison to HNG. Specifically, HGC showed 3- and 2.5-fold net increase in chondroitin sulphate (CS) and hyaluronan (HA) contents, respectively. Dermatan sulphate (DS) was slightly increased, but the amount of heparan sulphate (HS) was decreased. Of particular, interest were the quite different sulphation profiles of CS and DS chains in HGC in which, non-sulphated and 6-sulphated disaccharide units were increased 10 and 4 times, respectively, in comparison to HNG. On PG level, three different populations were identified in both HNG and HGC, being HSPGs, versican (CS/DS chains) and decorin (CS/DS chains). In HGC, the amounts of versican and decorin were significantly increased about 3- and 8-fold, respectively. These PGs were also characterized by marked decrease in hydrodynamic size and GAG content per PG molecule. Analysis of Delta-disaccharide of versican and decorin from HGC showed an increase of 6-sulphated Delta-disaccharides (Delta di-6S) and non-sulphated Delta-disaccharides (Delta di-0S) with a parallel decrease of 4-sulphated Delta-disaccharides (Delta di-4S) as compared to HNG, which closely correlated with the increase of CS content. In addition, the accumulation of core proteins of versican and decorin in HGC was also associated with many post-translational modifications, referring to the number, size, degree and patterns of sulphation and epimerization of CS/DS chains. Studies on the modified metabolism of PGs/GAGs are under progress and will help in deeper understanding of the environment in which tumor cells proliferate and invade.