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I. Brockhausen J. Yang, M. Lehotay, S. Ogata, S. Itzkowitz
Pathways of Mucin O-Glycosylation in Normal and Malignant Rat Colonic Epithelial Cells Reveal a Mechanism for Cancer-Associated Sialyl-Tn Antigen Expression
The SialylTn antigen (Sialyl?Ser/Thr) is expressed as a cancerassociated antigen on the surface of cancer cells. Its presence is associated with a poor prognosis in patients with colorectal and other cancers. We previously reported that SialylTn expression in LSC human colon cancer cells could be explained by a specific lack of the activity of core 1 ?3-Galtransferase (Brockhausen et al., Glycoconjugate J. 15, 595 603, 1998) and an inability to synthesize the common Oglycan core structures. To support this mechanism, or find other mechanisms to explain SialylTn antigen expression, we investigated the Oglycosylation pathways in clonal rat colon cancer cell lines that were selected for positive or negative expression of SialylTn antigen, and compared these pathways to those in normal rat colonic mucosa. Normal rat colonic mucosa had very active glycosyltransferases synthesizing Oglycan core structures 1 to 4. Several sialyl, sulfo and fucosyltransferases were also active. An M type core 2 ?6-GlcNActransferase was found to be present in rat colon mucosa and all of the rat colon cancer cells. Oglycosylation pathways in rat colon cancer cells were significantly different from normal rat colonic mucosa; for example, rat colon cancer cells lost the ability to synthesize Oglycan core 3. All rat colon cancer cell lines, regardless of the SialylTn phenotype, expressed glycosyltransferases assembling complex Oglycans of core 1 and core 2 structures (unlike human LSC colon cancer cells which lack core 1 ?3-Galtransferase activity). It was the activity of CMPsialic acid:GalNAcmucin ?6-sialyltransferase that coincided with SialylTn expression. SialylTn negative cells had a several fold higher activity of core 2 ?6-GlcNActransferase which synthesizes complex Oglycans that may mask adjacent SialylTn epitopes. The results suggest a new mechanism controlling SialylTn expression in cancer cells.
Biological Chemistry, Walter de Gruyter
Print ISSN: 1431-6730
Volume: 382, 03/2001
Pages: 219 - 232