Two 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 colorectal carcinoma cells. The O-linked oligosaccharides isolated from the glycophorins of Tn erythrocytes contained predominantly alpha-N-acetylgalactosamine-O-Ser/Thr (Tn antigen) and sialyl-Tn. A marked reduction in normal sialylated oligosaccharides was also observed. Monoclonal antibody BRIC 111 raised against Tn erythrocytes reacted with both Tn erythrocytes and colorectal carcinoma tissues. Weak staining was detected in the supranuclear area and at the surface membranes in normal colorectal cells, but was absent from goblet cell vesicles. An increase in supranuclear staining over controls was found in tumour tissue and in the majority of resection margin specimens. The highest levels of staining were present in transitional mucosa, adjacent to the tumours where goblet vesicles were also positive. Glycosylation defects in the same patients were further studied by determination of the activity of glycosyltransferases in mucosal tissue from control and cancer patients. The reduction in or loss of beta 1-3 N-acetylglucosaminyl transferase activity to GalNAc-peptide in asialo-ovine submaxillary gland glycoprotein was detected by direct assay and by isolation of the oligosaccharides from the incubation products. No differences in N-acetylglucosaminyl-, galactosyl- or sialyl-transfer to Gal beta 1-3GalNAc in antifreeze glycoprotein or in sialyl transferase to asialo-ovine submaxillary gland glycoprotein were detected. Our study shows that the GalNAc alpha-O-Ser/Thr determinant on Tn erythrocytes and in colorectal carcinoma results from different glycosyltransferase defects in separate biosynthetic pathways for haematopoietic and epithelial tissues.