Activity of the Human Blood Group ABO, Se, H, Le, and X Gene-encoded Glycosyltransferases in Normal and Malignant Bladder Urothelium¹

Immunohistochemistry has led to the finding of an expression of ABO-related blood group antigens in normal and malignant bladder urothelium which is different from that found on erythrocytes from the same individual. This includes a loss of blood group ABO expression in malignant urothelium, and the expression of Le^b antigens in normal and malignant cells from individuals with Le(a+b-) and Le(a-b-) erythrocytes. To elucidate the mechanism of this blood group antigen expression in urothelium we have analyzed the activity of the specific glycosyltransferases encoded by the ABO, Se, H, Le, and X blood group genes in normal and malignant urothelium. Biopsies of normal urothelium were obtained from 22 individuals and biopsies of urothelial tumors from 20 individuals. The tissue donors were typed for ABO, Lewis, and secretor status on erythrocytes and saliva. The biopsies were disaggregated to single cell suspensions, and the activity of the individual glycosyltransferases was determined as pmol of labeled sugar incorporated by oligosaccharide acceptors per 100,000 cells. The A (α-3-N-acetyl-d-galactosaminyl) and B (α-3-d-galactosyl) gene-specified transferases showed no activity in malignant cells, whereas all other enzymes examined were expressed in both normal and malignant cells. Secretors and nonsecretors showed the same α-2-l-fucosyltransferase activity in both normal and malignant cells, whereas the α-3-l-fucosyltransferase was reduced (P < 0.02) in malignant cells from Lewis positive individuals. The Lewis gene-encoded α-4-l-fucosyl-transferase showed a similar activity in Lewis positive and negative individuals. These results indicate that the disappearance of A and B blood group antigens in bladder tumors and the expression of Le^b antigens in normal and malignant cells from individuals with Le(a+b-) and Le(a-b-) erythrocytes are due to corresponding differences in glycosyltransferases. The results indicate that the ABO, H, Se, and Le genes are subjected to a tissue-dependent differential expression.