IMR Press / FBE / Volume 3 / Issue 4 / DOI: 10.2741/E345

Frontiers in Bioscience-Elite (FBE) is published by IMR Press from Volume 13 Issue 2 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Article
ST6GalNAc-I controls expression of sialyl-Tn antigen in gastrointestinal tissues
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1 Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), 4200 Porto, Portugal
2 Copenhagen Center for Glycomics (CCG), School of Dentistry and Department of Cellular and Molecular Medicine, University of Copenhagen, DK2200 Copenhagen, Denmark
3 Medical Faculty of the University of Porto, 4200 Porto, Portugal
4 Neose Technologies, Horsham, PA, USA
5 Department of Pathology, Rigshospitalet, Copenhagen University Hospital, Denmark
6 The Cancer Center and Department of Pathology, Oslo University Hospital, Ullevaal, 0407 Oslo, Norway
7 Breast Cancer Biology, King’s College London, London, UK

*Author to whom correspondence should be addressed.

 

Front. Biosci. (Elite Ed) 2011, 3(4), 1443–1455; https://doi.org/10.2741/E345
Published: 1 June 2011
Abstract

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 over-expressed 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.

Keywords
ST6GalNAc-I
Sialyl-Tn
Glycosylation
Gastric Carcinoma
Intestinal Metaplasia
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