The pattern of glycosyl-and sulfotransferase activities in cancer cell lines:a predictor of individual cancer-associated distinct carbohydrate structures for the structural identification of signature glycans

摘要

Carbohydrate chains of cancer glycoprotein antigens contain major outer changes dictated by tissue-specific regulation of glycosyltransferase genes,the availability of sugar nucleotides,and competition between enzymes for acceptor intermediates during glycan elongation.However,it is evident from recent studies with recombinant mucin probes that the final glycosylation profiles of mucin glycoproteins are mainly determined by the cellular repertoire of glycosyltransferases.Hence,we examined various cancer cell lines for the levels of fucosyl-,beta-galactosyl,beta-N-acetylgalactosaminyl-,sialyl-,and sulfotransferase activities that generate the outer ends of the oligosaccharide chains.We have identified glycosyltransferases activities at the levels that would give rise to O-glycan chains as reported by others in breast cancer celllines,T47D,ZR75-1,MCF-7,and MDA-MB-231.Most breast cancer cells express Gal-3-O-sulfotransferase specific for T-hapten Gal beta1->3GalNAco alpha-,whereas the enzyme from colon cancer cells exhibits a vast preference for the Gal beta1,4GlcNAc terminal unit in O-glycans.We also studied ovarian cancer cells SW626 and PA-1 and hepatic cancer cells HepG_2.Our studies show that alha1,2-L-fucosyl-T,alpha(2,3)sialyl-T,and 3-O-Sulfo-T capable of acting on the mucin core 2 tetrasaccharide,Gal beta1,4GlcNAc beta1,6(Gal beta1,3)GalNAc alpha-,can also act on the Globo H antigen backbone,Gal beta1,3GalNAc beta1,3Gal alpha-,suggesting the existence of unique carbohydrate moieties in certain cancer-associated glycolipids.Briefly,our study indicates the following:(i)3'-Sulfo-T-hapten has an apparent relationship to the tumorigenic potential of breast cancer cells;(ii)the 3'-sulfo Lewis~x,the 3-O-sulfo-Globo unit,and the 3-fucosylchitobiose core could be uniquely associated with colon cancer cells;(iii)synthesis of a polylactosamine chain and T-hapten are favorable in ovarian cancer cells due to negligible sialyltrans-ferase activities;and (iv)a 6'-sialyl LacNAc unit and 3'-sialyl T-hapten appear to be prevalent structures in hepatic cancer cell glycans.Thus,it is apparent that different cancer cells are expressing unique glycan epitopes,which could be novel targets for cancer diagnosis and treatment.