α2→3Sialyltransferase associated with the synthesis of CA 19‐9 in colorectal tumors

Abstract

BACKGROUND A novel assay method specific for α2→3sialyltransferase that seems to be responsible for the synthesis of CA 19-9 antigen was developed and the levels of the enzyme in colorectal tumor tissues were measured and compared with the levels of α1→4fucosyltransferase and the CA 19-9 antigen. METHODS Lacto-N-biose I (Galβ1→3GlcNAcβ, Lewisc [Lec]) and 6-O-methyl-Lec(Galβ1→3[6OMe]GlcNAcβ) were synthesized and covalently attached to bovine serum albumin (BSA). These two substrates were incubated with extracts from colorectal tissues in the presence of cytidine 5′-monophospho-N-acetylneuraminic acid (CMP-NeuAc) and their resulting products were detected by a sequential use of anti-BSA monoclonal antibody-coated beads and 125I-labelled anti-sialylated Lec antibody. Levels of α2→3sialyltransferase and α1→4fucosyltransferase activities and CA 19-9 antigen were measured in the extracts from colorectal tumors and their adjacent normal tissues. RESULTS 6-O-Methyl-Lec-BSA showed a strong acceptor activity compared with Lec-BSA and was used as a specific acceptor for α2→3sialyltransferase. Similar elevation patterns of α2→3sialyltransferase activities and CA 19-9 antigen levels were observed in tumor extracts but no clear correlation was present between the level of α1→4fucosyltransferase activities and CA 19-9 antigen levels in the same extracts. CONCLUSIONS The accumulation of CA 19-9 antigen in colorectal tumors might be caused mainly by the activation of α2→3sialyltransferase but not by that of α1→4fucosyltransferase. Cancer 1996;77:1694-700.