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.
authors.affiliation: Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal.
authors.forename: Nuno T
authors.initials: NT
authors.lastname: Marcos
authors.forename: Eric P
authors.initials: EP
authors.lastname: Bennett
authors.forename: Joana
authors.initials: J
authors.lastname: Gomes
authors.forename: Ana
authors.initials: A
authors.lastname: Magalhaes
authors.forename: Catarina
authors.initials: C
authors.lastname: Gomes
authors.forename: Leonor
authors.initials: L
authors.lastname: David
authors.forename: Imran
authors.initials: I
authors.lastname: Dar
authors.forename: Charlotte
authors.initials: C
authors.lastname: Jeanneau
authors.forename: Shawn
authors.initials: S
authors.lastname: DeFrees
authors.forename: Dorrit
authors.initials: D
authors.lastname: Krustrup
authors.forename: Lotte K
authors.initials: LK
authors.lastname: Vogel
authors.forename: Elin H
authors.initials: EH
authors.lastname: Kure
authors.forename: Joy
authors.initials: J
authors.lastname: Burchell
authors.forename: Joyce
authors.initials: J
authors.lastname: Taylor-Papadimitriou
authors.forename: Henrik
authors.initials: H
authors.lastname: Clausen
authors.forename: Ulla
authors.initials: U
authors.lastname: Mandel
authors.forename: Celso A
authors.initials: CA
authors.lastname: Reis
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015295:Antigens, Tumor-Associated, Carbohydrate; D001483:Base Sequence; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D017931:DNA Primers; D041981:Gastrointestinal Tract / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D012799:Sialyltransferases / Q000276:immunology / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D015295:Antigens, Tumor-Associated, Carbohydrate; D017931:DNA Primers; C055491:sialosyl-Tn antigen; D012799:Sialyltransferases