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

Nuno T Marcos; Eric P Bennett; Joana Gomes; Ana Magalhaes; Catarina Gomes; Leonor David; Imran Dar; Charlotte Jeanneau; Shawn Defrees; Dorrit Krustrup; Lotte K Vogel; Elin H Kure; Joy Burchell; Joyce Taylor-Papadimitriou; Henrik Clausen; Ulla Mandel; Celso A Reis

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

Nuno T Marcos, Eric P Bennett, Joana Gomes, Ana Magalhaes, Catarina Gomes, Leonor David, Imran Dar, Charlotte Jeanneau, Shawn Defrees, Dorrit Krustrup, Lotte K Vogel, Elin H Kure, Joy Burchell, Joyce Taylor-Papadimitriou, Henrik Clausen, Ulla Mandel, Celso A Reis

79 Citations (Scopus)

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.

Original language	English
Journal	Frontiers in Bioscience (Elite Edition)
Volume	3
Pages (from-to)	1443-55
Number of pages	13
ISSN	1945-0494
Publication status	Published - 6 Jan 2011

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Marcos, N. T., Bennett, E. P., Gomes, J., Magalhaes, A., Gomes, C., David, L., Dar, I., Jeanneau, C., Defrees, S., Krustrup, D., Vogel, L. K., Kure, E. H., Burchell, J., Taylor-Papadimitriou, J., Clausen, H., Mandel, U., & Reis, C. A. (2011). ST6GalNAc-I controls expression of sialyl-Tn antigen in gastrointestinal tissues. Frontiers in Bioscience (Elite Edition), 3, 1443-55.

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title = "ST6GalNAc-I controls expression of sialyl-Tn antigen in gastrointestinal tissues",

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.",

author = "Marcos, {Nuno T} and Bennett, {Eric P} and Joana Gomes and Ana Magalhaes and Catarina Gomes and Leonor David and Imran Dar and Charlotte Jeanneau and Shawn Defrees and Dorrit Krustrup and Vogel, {Lotte K} and Kure, {Elin H} and Joy Burchell and Joyce Taylor-Papadimitriou and Henrik Clausen and Ulla Mandel and Reis, {Celso A}",

year = "2011",

month = jan,

day = "6",

language = "English",

volume = "3",

pages = "1443--55",

journal = "Frontiers in Bioscience - Elite",

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TY - JOUR

T1 - ST6GalNAc-I controls expression of sialyl-Tn antigen in gastrointestinal tissues

AU - Marcos, Nuno T

AU - Bennett, Eric P

AU - Gomes, Joana

AU - Magalhaes, Ana

AU - Gomes, Catarina

AU - David, Leonor

AU - Dar, Imran

AU - Jeanneau, Charlotte

AU - Defrees, Shawn

AU - Krustrup, Dorrit

AU - Vogel, Lotte K

AU - Kure, Elin H

AU - Burchell, Joy

AU - Taylor-Papadimitriou, Joyce

AU - Clausen, Henrik

AU - Mandel, Ulla

AU - Reis, Celso A

PY - 2011/1/6

Y1 - 2011/1/6

N2 - 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.

AB - 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.

M3 - Journal article

C2 - 21622148

SN - 1945-0494

VL - 3

SP - 1443

EP - 1455

JO - Frontiers in Bioscience - Elite

JF - Frontiers in Bioscience - Elite

ER -

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

Abstract

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