Core 3 synthase is down-regulated in colon carcinoma and profoundly suppresses the metastatic potential of carcinoma cells

Abstract

The core 3 structure of the O -glycan, GlcNAcβ1-3GalNAcα1-Ser/Thr, an important precursor in the biosynthesis of mucin-type glycoproteins, is synthesized by β1,3- N -acetylglucosaminyltransferase 6 (β3Gn-T6; core 3 synthase). We generated an anti-β3Gn-T6 mAb (G8-144 mAb) and performed immunohistochemical analyses. In normal stomach and colon, β3Gn-T6 was strongly expressed in the Golgi region of epithelia. In contrast, its expression was markedly down-regulated in gastric and colorectal carcinomas. Tissue specimens from a familial adenomatous polyposis patient showed a clear correlation between the down-regulation of β3Gn-T6 expression and the degree of dysplasia/neoplasia. In vitro , the level of β 3Gn-T6 transcript was increased according to the differentiation of Caco-2 cells. These results suggested that the expression of β3Gn-T6 is closely regulated during differentiation and dedifferentiation. β3Gn-T6 would be a useful marker for distinguishing between benign adenomas and premalignant lesions. HT1080 FP-10 cells stably transfected with the β 3Gn-T6 gene showed a decrease in the core 1 structure, Galβ1,3GalNAcα1-Ser/Thr, probably due to competition between the core 1 synthase and core 3 synthase. The migration activity of the transfectants was markedly lower than that of mock transfectants in vitro , and lung metastasis after i.v. injection of the transfectants into nude mice was significantly suppressed. These findings indicated that the core structures of O -glycans are profoundly involved in the metastatic capacity of cancer cells.