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.