ST6GalNAc-I controls expression of sialyl-Tn antigen in gastrointestinal tissues
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ST6GalNAc-I controls expression of sialyl-Tn antigen in gastrointestinal tissues. / Marcos, Nuno T; Bennett, Eric P; Gomes, Joana; Magalhaes, Ana; Gomes, Catarina; David, Leonor; Dar, Imran; Jeanneau, Charlotte; Defrees, Shawn; Krustrup, Dorrit; Vogel, Lotte K; Kure, Elin H; Burchell, Joy; Taylor-Papadimitriou, Joyce; Clausen, Henrik; Mandel, Ulla; Reis, Celso A.
I: Frontiers in Bioscience (Elite Edition), Bind 3, 01.06.2011, s. 1443-55.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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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 - 2011/6/1
Y1 - 2011/6/1
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
VL - 3
SP - 1443
EP - 1455
JO - Frontiers in Bioscience - Elite
JF - Frontiers in Bioscience - Elite
SN - 1945-0494
ER -
ID: 33751119