Galactosyltransferase associated with tumor in patients with ovarian cancer: factors involved in elevation of serum galactosyltransferase.
The serum level of beta1,4-galactosyltransferase (beta1,4-GalT) is increased in both malignancy and benign diseases. Galactosyltransferase associated with tumor (GAT) is one of the soluble forms of beta1,4-GalT, and is a marker of ovarian cancer with a high specificity. GAT and normal soluble beta1,4-GalT are both derived from the same membrane-bound form of the enzyme. This study investigated the mechanism of GAT elevation in patients with ovarian cancer. The serum levels of GAT and normal beta1,4-GalT were measured using specific monoclonal antibodies. In addition, nude mice bearing human ovarian cancer were used to assess the kinetics of tumor-derived enzymes. GAT and normal beta1,4-GalT were both detected in ovarian cancer patients, but only GAT reflected the tumor status. In tumor-bearing nude mice, both soluble forms of beta1,4-GalT were released from tumor cells, but the half-life of GAT was far shorter than that of normal beta1,4-GalT. Addition of serum from healthy women to colostrum (which has a high GAT content) reduced the GAT level, while adding patient serum caused a significantly smaller reduction of GAT. Addition of the serum from mouse which includes no human beta1,4-GalT to colostrum also reduced the GAT level with no significant change of total soluble beta1,4-GalT. These findings indicate that human serum contains certain factors that decrease the GAT level, but these factors are inhibited in ovarian cancer patients so that a high GAT level persists. It seems that the decrease of GAT occurs as a result of conversion into normal beta1,4-GalT.
Saitoh
Eiko
E
Department of Obstetrics and Gynecology, School of Medicine, Keio University, Tokyo 160-8582, Japan.
Aoki
Daisuke
D
Susumu
Nobuyuki
N
Udagawa
Yasuhiro
Y
Nozawa
Shiro
S
D000818:Animals; D014408:Biomarkers, Tumor / Q000097:blood* / Q000235:genetics; D015152:Blotting, Northern; D003126:Colostrum / Q000201:enzymology; D005260:Female; D005700:Galactosyltransferases / Q000097:blood / Q000235:genetics; D006801:Humans; D007124:Immunoenzyme Techniques; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D009237:N-Acetyllactosamine Synthase / Q000097:blood* / Q000235:genetics; D009374:Neoplasms, Experimental / Q000201:enzymology; D010051:Ovarian Neoplasms / Q000201:enzymology*; D012333:RNA, Messenger / Q000378:metabolism; D014407:Tumor Cells, Cultured
D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D005700:Galactosyltransferases; D009237:N-Acetyllactosamine Synthase