Potential tumor markers for human gastric cancer: an elevation of glycan:sulfotransferases and a concomitant loss of alpha1,2-fucosyltransferase activities.

Purpose: Several reports indicate a complexity in glycosyltransferase activities which lead to several tumor associated carbohydrate structures in gastric carcinoma. The present study was aimed to identify the carbohydrate associated transferases which exhibit the most marked and consistent change of activity in gastric tumorigenesis.

Methods: We examined the levels of fucosyl, beta-galactosyl-, beta-N-acetylgalactosaminyl, sialyl- and glycan:sulfotransferase activities, which generate the outer ends of oligosaccharide chains in tumorous and adjacent normal gastric tissues of the same patient in ten gastric carcinoma cases by using well defined specific synthetic acceptors utilized in our several earlier published studies as referenced in the text (e.g. Chandrasekaran et al. in J Biol Chem 279:10032-10041, 2004; Biochemistry 44:15619-15635, 2005; Carbohydr Res 341:983-994, 2006).

Results: Among glycosyltransferases only alpha1,2-fucosyltransferase (FT) was unique in showing a remarkable 40-90% decrease of activity in seven cases. Uniquely several fold elevation of Gal3Sulfo-T(2) (1.9 --> 156.7 fold) and Gal3Sulfo-T(4) (2.4 --> 149.0 fold) activities in all ten cases and moderate elevation of GlcNAc6Sulfo-T (1.3 --> 37.5 fold) activities in nine cases were identified. Poorly differentiated Signet ring cell carcinoma expresses mainly Gal3Sulfo-T(2) activity whereas poorly differentiated adenocarcinoma express predominantly Gal3Sulfo-T(4) activity and also GlcNAc6Sulfo-T activity. But, very low level of these sulfotransferase activities were identified in moderately differentiated gastric carcinomas as well as non-epithelial gastric stromal sarcoma.

Conclusion: Up regulation of glycan:sulfotransferase activities and down regulation of alpha1,2-fucosyltransferase activity are apparently associated with human gastric tumorigenesis.