INHIBITION OF MUCIN SYNTHESIS BY BENZYL-ALPHA-GALNAC IN KATO-III GASTRIC-CANCER AND CACO-2 COLON-CANCER CELLS

Previous studies from our laboratory have shown that benzyl-alpha-GalN Ac inhibits the glycosylation of mucin in colon cancer cells. In this study, we determined whether benzyl-alpha-GalNAc inhibits mucin glycos ylation in KATO III gastric cancer cells. We also examined its effects on expression of mucin antigens, and compared the mucins made by KATO III with those of a colonic cancer cell line, Caco-2. Results of thes e experiments suggest that benzyl-alpha-GalNAc (2 mM) inhibited [H-3]g lucosamine labelling of mucins by 82% in KATO III and by 70% in Caco-2 . For both cell lines, the mucin secreted in the presence of benzyl-al pha-GalNAc was less acidic. Both cell lines secreted benzyl-oligosacch arides, but those from KATO III (8-9 sugars) were larger than those fr om Caco-2 (6-7 sugars). In mucins purified from the medium of treated cells, peripheral carbohydrate antigens (sialyl Le(x) in KATO III and terminal fucose in Caco-2) were decreased (compared with control), whi le core carbohydrate antigens (T antigen in both cell lines and sialyl Tn in Caco-2) were increased. Western blots of cell homogenates showe d differences between KATO III and Caco-2 in MUC 1 apomucin protein an tigens, in sialyl Le(x) and in sialyl Tn antigens. We conclude that be nzyl-alpha-GalNAc does inhibit the glycosylation of mucin in KATO III gastric cancer cells as in human colon cancer cells, but that alterati ons in mucin antigens occur in a cell line-specific manner.