ST6GalNAc-I controls expression of sialyl-Tn antigen in gastrointestinal tissues

• Type: Article in International Scientific Journal
• Date: 2011

Authors

Marcos, NT (Author) Other; Bennett, EP (Author) Other; Gomes, J (Author) Other; Magalhaes, A (Author) Other; Gomes, C (Author) Other; David L (Author) FMUP; Dar, I (Author) Other; Jeanneau, C (Author) Other; DeFrees, S (Author) Other; Krustrup, D (Author) Other; Vogel, LK (Author) Other; Kure, EH (Author) Other; Burchell, J (Author) Other; Taylor Papadimitriou, J (Author) Other; Clausen, H (Author) Other; Mandel, U (Author) Other; Celso Reis (Author) ICBAS

Journal

Title: Frontiers in Bioscience - Elite

Vol. 3 E

Pages: 1443-1455

ISSN: 1945-0494

Publisher: Frontiers in Bioscience

Indexing

Scopus - 90 Citations

Other information

Authenticus ID: P-008-0K6

Abstract (EN): Sialyl-Tn is a simple mucin-type carbohydrate antigen aberrantly expressed in gastrointestinal adenocarcinomas and in the precursor lesion intestinal metaplasia. Sialyl-Tn tumour expression is an independent indicator of poor prognosis. We have previously shown in vitro that ST6GalNAc-I and ST6GalNAc-II sialyltransferases can synthesize sialyl-Tn. The aim of the present study was to establish whether ST6GalNAc-I is the major enzyme responsible for the expression of sialyl-Tn. We used a model of CHO-ldlD cells producing only MUC1-Tn glycoform and showed that ST6GalNAc-I is the key-enzyme leading to sialyl-Tn biosynthesis. We developed novel monoclonal antibodies specific for ST6GalNAc-I and evaluated its expression in gastrointestinal tissues. ST6GalNAc-I was detected in normal colon mucosa co-localized with O-acetylated sialyl-Tn. Expression was largely unaltered in colorectal adenocarcinomas. In contrast, we found that ST6GalNAc-I is weakly expressed in normal gastric mucosa, but overexpressed in intestinal metaplasia, co-localized with sialyl-Tn. In gastric carcinomas ST6GalNAc-I was also associated with sialyl-Tn, but with heterogeneous staining and partial co-localization. Our results showed ST6GalNAc-I as the major enzyme controlling the expression of cancer-associated sialyl-Tn antigen in gastrointestinal tissues.

Language: English

Type (Professor's evaluation): Scientific