Alpha 2-->3sialyltransferase associated with the synthesis of CA 19-9 in colorectal tumors.
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.
Akamatsu
S
S
Diagnostic Division, Otsuka Pharmaceutical Company, Ltd., Tokushima, Japan.
Yazawa
S
S
Tachikawa
T
T
Furuta
T
T
Okaichi
Y
Y
Nakamura
J
J
Asao
T
T
Nagamachi
Y
Y
D000117:Acetylglucosamine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000378:metabolism; D000818:Animals; D018395:CA-19-9 Antigen / Q000096:biosynthesis*; D002240:Carbohydrate Sequence; D002417:Cattle; D015179:Colorectal Neoplasms / Q000097:blood / Q000201:enzymology / Q000378:metabolism*; D005647:Fucosyltransferases / Q000378:metabolism; D006801:Humans; D007983:Lewis Blood Group Antigens; D008969:Molecular Sequence Data; D010641:Phenotype; D012799:Sialyltransferases / Q000378:metabolism*; D000094663:beta-Galactoside alpha-2,3-Sialyltransferase
D018395:CA-19-9 Antigen; D007983:Lewis Blood Group Antigens; C033398:galactosyl-1,3-N-acetylglucosamine; D005647:Fucosyltransferases; C019818:3-galactosyl-N-acetylglucosaminide 4-alpha-L-fucosyltransferase; D012799:Sialyltransferases; D000117:Acetylglucosamine; D000094663:beta-Galactoside alpha-2,3-Sialyltransferase