2 DIFFERENT GLYCOSYLTRANSFERASE DEFECTS THAT RESULT IN GALNAC-ALPHA-O-PEPTIDE (TN) EXPRESSION

This study shows for the first time that different glycosyltransferase defects in the biosynthesis of O-linked oligosaccharides give rise to the same GalNAc alpha-O-Ser/Thr determinant on Tn erythrocytes and co lorectal carcinoma cells. The O-linked oligosaccharides isolated from the glycophorins of Tn erythrocytes contained predominantly alpha-N-ac etylgalactosamine-O-Ser/Thr (Tn antigen) and sialyl-Tn. A marked reduc tion in normal sialylated oligosaccharides was also observed. Monoclon al antibody BRIC 111 raised against Tn erythrocytes reacted with both Tn erythrocytes and colorectal carcinoma tissues. Weak staining was de tected in the supranuclear area and at the surface membranes in normal colorectal cells, but was absent from goblet cell vesicles. An increa se in supranuclear staining over controls was found in tumour tissue a nd in the majority of resection margin specimens. The highest levels o f staining were present in transitional mucosa, adjacent to the tumour s where goblet vesicles were also positive. Glycosylation defects in t he same patients were further studied by determination of the activity of glycosyltransferases in mucosal tissue from control and cancer pat ients. The reduction in or loss of beta 1-3 N-acetylglucosaminyl trans ferase activity to GalNAc-peptide in asialo-ovine submaxillary gland g lycoprotein was detected by direct assay and by isolation of the oligo saccharides from the incubation products. No differences in N-acetylgl ucosaminyl-, galactosyl- or sialyl-transfer to Gal beta 1-3GalNAc in a ntifreeze glycoprotein or in sialyl transferase to asialo-ovine submax illary gland glycoprotein were detected. Our study shows that the GalN Ac alpha-O-Ser/Thr determinant on Tn erythrocytes and in colorectal ca rcinoma results from different glycosyltransferase defects in separate biosynthetic pathways for haematopoietic and epithelial tissues.