Alterations of O-glycan biosynthesis in human colon cancer tissues

Human colon cancer is associated with antigenic and structural changes in mucin-type carbohydrate chains (O-glycans). To elucidate the control of the biosynthesis of these O-glycans in colon cancer, we have studied glycosyltransferase and sulphotransferase activities involved in the assembly of elongated O-glycan structures. We analysed homogenates prepared from cancer tissue, adjacent normal and distal normal tissue from 20 patients. Several transferase activities showed pronounced changes in cancer tissue. The changes correlate with previous findings of a loss of O-glycans in cancer mucins, but did not always correlate with levels of Tn, sialyl-Tn, T and Le^x antigens in homogenates or with the differentiation status and Duke's stages of the cancer tissue or the patient's blood type, sex and age. UDP-GlcNAc: Gal NAc-R β3-N-acetylglucosaminyltransferase (where GlcNAc is N-acetyl-D-glucosamine and GalNAc is N-acetyl-D-galactosamine) synthesizing O-glycan core 3, GlcNAcβ1-3GalNAc-, CMP-sialic acid: GalNAc-peptide α6-sialyltransferase synthesizing the sialyl-Tn antigen and sulphotransferase activities towards O-glycan core 1, Galβ1-3GalNAc-, were found to be decreased in cancer. UDP-GlcNAc: Galβ1-3GalNAc β6-N-acetylglucosaminyltransferase was also decreased in cancer concomitant with a loss of the ability to synthesize the I antigen and core 4, GlcNAcβ1-6(GlcNAcβ1-3) GalNAc-. CMP-sialic acid: Galβ1-3GalNAc-R α3-sialyltransferase and GDP-fucose: Galβ-R α2-fucosyltransferase, synthesizing the blood group H determinant, were found to be 4- and 3- to 8-fold increased, respectively, in cancer compared to normal tissue. The data suggest that the biosynthesis of antigens and mucin-bound O-glycan structures in colon cancer is subject to complex control mechanisms.