Galactosyltransferase associated with tumor in patients with ovarian cancer: Factors involved in elevation of serum galactosyltransferase

Abstract

The serum level of ß1,4-galactosyltransferase (ß1,4-GalT) is increased in both malignancy and benign diseases. Galactosyltransferase associated with tumor (GAT) is one of the soluble forms of ß1,4-GalT, and is a marker of ovarian cancer with a high specificity. GAT and normal soluble ß1,4-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 ß1,4-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 ß1,4-GalT were both detected in ovarian cancer patients, but only GAT reflected the tumor status. In tumor-bearing nude mice, both soluble forms of ß1,4-GalT were released from tumor cells, but the half-life of GAT was far shorter than that of normal ß1,4-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 ß1,4-GalT to colostrum also reduced the GAT level with no significant change of total soluble ß1,4-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 ß1,4-GalT.

Time-Dependent Structural Alteration of Rituximab Analyzed by LC/TOF-MS after a Systemic Administration to Rats

“…Although rituximab slightly underwent structural transitions in the rat body, no significant differences in both CDC and ADCC activities were observed up to 21 days after systemic administration. However, there are some plausible reports that serum level of galactosyltransferase associated with tumor increases in patients with bladder [34] and ovarian cancer [35]. Besides, the expression level of fucosyltransferase IV, which is involved in the altered glycosylation of cancer, has significantly increased in breast cancer tissues and serum [36].…”

TINAGL1 and B3GALNT1 are potential therapy target genes to suppress metastasis in non-small cell lung cancer

“…S8 (Additional file 4 ) shows the tertiary structure of B3GALNT1 as predicted by FAMS. Numerous studies have suggested a relationship between galactosyl transferase and cancer, including the use of galactosyl transferase as a tumor biomarker for ovarian clear cell carcinoma [ 27 , 28 ]. Alternatively, cancer-associated isoenzymes of serum galactosyl transferase were reported in various cancers [ 29 ].…”

The Serum Glycome to Discriminate between Early-Stage Epithelial Ovarian Cancer and Benign Ovarian Diseases

“…The sialyl Lewis X antigen is carried by acute-phase glycoproteins that circulate in serum of patients suffering from inflammatory conditions: α -1 acid glycoprotein, haptoglobin, and α 1-antichymotrypsin [ 45 ]. In addition, the upregulation of the corresponding glycosyltransferases was also measured in the serum of ovarian cancer patients: ( α 1-3) fucosyltransferase [ 46 ], ( β 1-4) galactosyltransferase [ 47 ], and ( α 2-6) sialyltransferase [ 48 , 49 ].…”