Fucosyltransferase and alpha-L-fucosidase activities and fucose levels in normal and malignant endometrial tissue.
Previous immuno- and lectin-histochemical studies using mAbs and Ulex europaeus lectin I, which recognize various fucose-containing blood group antigens, have shown an increased expression of Lewis and H blood group antigens in endometrial carcinoma. We investigated the biochemical basis of aberrant fucose-containing antigen expression by comparing the activity of fucosyltransferases (FTase) and alpha-L-fucosidase in tissue biopsies from normal (n = 18) and malignant (n = 20) endometrium. Alteration of FTase activity in tumor tissue homogenates was evaluated by using a panel of FTase substrates including N-acetyllactosamine (type 2), lacto-N-biose I (type 1), and phenyl-beta-D-galactoside. Based on histological subtyping, the endometrioid group (n = 14) showed a significant (P < 0.05) increase in tumor FTase activity with all three substrates, while no significant increase was detected for the papillary serous group (n = 4). Matched pair analysis of normal and tumor tissue from a subgroup (n = 5) of the patients with increased tumor enzyme activity also showed higher FTase activity (P < 0.05) in the tumor tissue when the type 1 substrate was used. Regression analysis showed a correlation between the FTase activities acting on type 2 or type 1 substrates (r = 0.821 and r = 0.722, respectively) and the endogenous fucose levels in tumor homogenates. Spectrophotometric analysis of alpha-L-fucosidase activity using p-nitrophenyl-alpha-L-fucoside revealed a higher activity in tumor homogenates than in normal homogenates (P < 0.05) and, therefore, could not account for the enhanced expression of fucose-containing antigens. The current study suggests that aberrant expression of fucose-containing antigens, such as the H and the Lewis blood-group antigens, in endometrial carcinoma is consequential to the change in FTase rather than in alpha-L-fucosidase activity. In addition, the investigation suggests that different glycosylation mechanisms are operative in different subtypes of endometrial cancer.
Wang
J W
JW
Department of Pathology and Laboratory Medicine, Albany Medical Center, New York 12208-3478, USA.
Ambros
R A
RA
Weber
P B
PB
Rosano
T G
TG
D000017:ABO Blood-Group System / Q000378:metabolism; D000328:Adult; D000368:Aged; D002277:Carcinoma / Q000196:embryology*; D016889:Endometrial Neoplasms / Q000378:metabolism*; D004717:Endometrium / Q000378:metabolism*; D005260:Female; D005643:Fucose / Q000378:metabolism*; D005647:Fucosyltransferases / Q000378:metabolism*; D006801:Humans; D007983:Lewis Blood Group Antigens / Q000378:metabolism; D008875:Middle Aged; D005644:alpha-L-Fucosidase / Q000378:metabolism*
D000017:ABO Blood-Group System; D007983:Lewis Blood Group Antigens; D005643:Fucose; D005647:Fucosyltransferases; D005644:alpha-L-Fucosidase