Fucosyltransferase-producing sialyl Le(a) and sialyl Le(x) carbohydrate antigen in benign and malignant gastrointestinal mucosa.
BACKGROUND
Sialyl Le(a) antigen and sialyl Le(x) antigen are cancer-associated carbohydrate antigens. Previous immunohistologic and immunochemical studies have shown that these antigens are preferentially expressed in gastric cancer and colonic cancer and that they possibly are related to the metastatic potential of the cancer cells. The biosynthesis of these antigens is completed by fucosyltransferases, but it has not been reported how fucosyltransferases control the expression of these carbohydrate antigens concerning the invasive potential of the cancer.


METHODS
The authors established an assay system for measuring the activity of alpha 1-->4 fucosyltransferase (sialyl Le(a) synthase) and alpha 1-->3 fucosyltransferase (sialyl Le(x) synthase) with a high-pressure liquid chromatography system (HPLC). The activity was measured in various parts of normal and cancerous gastric and colonic tissue and compared with the expression of sialyl Le(a), sialyl Le(x), Le(a), and Le(x) antigens determined in a solid-phase enzyme-linked immunosolvent assay (EIA).


RESULTS
Sialyl Le(a) synthase was detected in most normal or malignant mucosa of gastric and colonic tissues, regardless of anatomic locations. Sialyl Le(x) synthase activity generally was low in the normal gastric mucosa, whereas the activity was higher in 77% (7 of 9) of gastric cancer tissues than in corresponding normal tissues with enhanced expression of sialyl Le(x) antigen in most patients (5 of 7). In the large intestine, the activity of sialyl Le(a) synthase and sialyl Le(x) synthase was correlated. Although enhanced expression of sialyl Le(x) in colonic cancer was observed in 86% (12 of 14) of all patients, concomitant higher sialyl Le(x) synthase activity than that in normal tissue was observed in only 58% (7 of 12) of patients.


CONCLUSIONS
The expression of sialyl Le(a) and sialyl Le(x) antigens in the stomach and the colon was not controlled solely by fucosyltransferases but by a more complicated system involving other glycosyltransferases.
Dohi
T
T
Division of Biochemistry and Nutrition, Research Institute, Tokyo, Japan.
Hashiguchi
M
M
Yamamoto
S
S
Morita
H
H
Oshima
M
M
D000230:Adenocarcinoma / Q000737:chemistry / Q000235:genetics; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000032:analysis* / Q000235:genetics; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D018395:CA-19-9 Antigen; D003110:Colonic Neoplasms / Q000737:chemistry / Q000235:genetics; D005647:Fucosyltransferases / Q000032:analysis* / Q000235:genetics; D005732:Gangliosides / Q000032:analysis* / Q000235:genetics; D005753:Gastric Mucosa / Q000737:chemistry* / Q000201:enzymology; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007413:Intestinal Mucosa / Q000737:chemistry / Q000201:enzymology; D007983:Lewis Blood Group Antigens / Q000032:analysis* / Q000235:genetics; D016256:Lewis X Antigen / Q000032:analysis* / Q000235:genetics; D009844:Oligosaccharides / Q000032:analysis / Q000235:genetics; D013274:Stomach Neoplasms / Q000737:chemistry* / Q000235:genetics; D013997:Time Factors; D014407:Tumor Cells, Cultured
D015295:Antigens, Tumor-Associated, Carbohydrate; D014408:Biomarkers, Tumor; D018395:CA-19-9 Antigen; D005732:Gangliosides; D007983:Lewis Blood Group Antigens; D016256:Lewis X Antigen; D009844:Oligosaccharides; C069719:sialosyl dimeric Le(x) antigen; C058981:sialyl-Le(a) oligosaccharide; C064564:sialyl Le(a) ganglioside; D005647:Fucosyltransferases; C019818:3-galactosyl-N-acetylglucosaminide 4-alpha-L-fucosyltransferase