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

Front Biosci (Elite Ed). 2011 Jun 1;3:1443-55. doi: 10.2741/e345.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology
  • Antigens, Tumor-Associated, Carbohydrate
  • Base Sequence
  • CHO Cells
  • Cricetinae
  • Cricetulus
  • DNA Primers
  • Gastrointestinal Tract / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Sialyltransferases / immunology
  • Sialyltransferases / metabolism*

Substances

  • Antibodies, Monoclonal
  • Antigens, Tumor-Associated, Carbohydrate
  • DNA Primers
  • sialosyl-Tn antigen
  • Sialyltransferases