Alpha 2-->3sialyltransferase associated with the synthesis of CA 19-9 in colorectal tumors.

Abstract

BACKGROUND:

A novel assay method specific for alpha 2-->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 alpha 1-->4fucosyltransferase and the CA 19-9 antigen.

METHODS:

Lacto-N-biose I (Gal beta 1-->3GlcNAc beta, Lewis(c) [Le(c)]) and 6-O-methyl-Le(c) (Gal beta 1-->3[6OMe]GlcNAc beta) 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 Le(c) antibody. Levels of alpha 2-->3sialyltransferase and alpha 1-->4fucosyltranferase activities and CA 19-9 antigen were measured in the extracts from colorectal tumors and their adjacent normal tissues.

RESULTS:

6-O-Methyl-Le(c)-BSA showed a strong acceptor activity compared with Le(c)-BSA and was used as a specific acceptor for alpha 2-->3sialyltransferase. Similar elevation patterns alpha 2-->3sialyltransferase activities and CA 19-9 antigen levels were observed in tumor extracts but no clear correlation was present between the level of alpha 1-->4fucosyltransferase activities and CA 19-9 antigen levels were observed in tumor extracts but no clear correlation was present between the level of alpha 1-->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 alpha 2-->3sialyltransferase but not by that of alpha 1-->fucosyltransferase.

• Authors: S Akamatsu, S Yazawa, T Tachikawa, T Furuta, Y Okaichi, J Nakamura, T Asao, Y Nagamachi
• Journal: Cancer (Cancer) Vol. 77 Issue 8 Suppl Pg. 1694-700 (Apr 15 1996) ISSN: 0008-543X [Print] United States
• PMID: 8608564 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CA-19-9 Antigen
• Lewis Blood Group Antigens
• galactosyl-1,3-N-acetylglucosamine
• Fucosyltransferases
• 3-galactosyl-N-acetylglucosaminide 4-alpha-L-fucosyltransferase
• Sialyltransferases
• Acetylglucosamine
• beta-Galactoside alpha-2,3-Sialyltransferase

Topics

• Acetylglucosamine (analogs & derivatives, chemical synthesis, metabolism)
• Animals
• CA-19-9 Antigen (biosynthesis)
• Carbohydrate Sequence
• Cattle
• Colorectal Neoplasms (blood, enzymology, metabolism)
• Fucosyltransferases (metabolism)
• Humans
• Lewis Blood Group Antigens
• Molecular Sequence Data
• Phenotype
• Sialyltransferases (metabolism)
• beta-Galactoside alpha-2,3-Sialyltransferase