Role of the human ST6GalNAc-I and ST6GalNAc-II in the synthesis of the cancer-associated sialyl-Tn antigen

• Type: Article in International Scientific Journal
• Date: 2004

Authors

Marcos, NT (Author) Other; Pinho, S (Author) Other; Grandela, C (Author) Other; Cruz, A (Author) Other; Samyn Petit, B (Author) Other; Harduin Lepers, A (Author) Other; Raquel Almeida (Author) Other; Silva, F (Author) Other; Morais, V (Author) Other; Costa, J (Author) Other; Kihlberg, J (Author) Other; Clausen, H (Author) Other; Celso Reis (Author) Other

Journal

The Journal is awaiting validation by the Administrative Services.

Title: CANCER RESEARCH

Vol. 64

Pages: 7050-7057

ISSN: 0008-5472

Indexing

ISI Web of Knowledge - 176 Citations

Scopus - 190 Citations

Other information

Authenticus ID: P-000-86C

DOI: 10.1158/0008-5472.can-04-1921

Abstract (EN): The Sialyl-Tn antigen (Neu5Acalpha2-6GaINAc-O-Ser/Thr) is highly expressed in several human carcinomas and is associated with carcinoma aggressiveness and poor prognosis. We characterized two human sialyltransferases,(CMP)-C-.-Neu5Ac:GaINAc-R alpha2,6-sialyltransferase (ST6GaINAc)-I and ST6GaINAc-II, that are candidate enzymes for Sialyl-Tn synthases. We expressed soluble recombinant hST6GaINAc-I and hST6GaINAc-II and characterized the substrate specificity of both enzymes toward a panel of glycopeptides, glycoproteins, and other synthetic glycoconjugates. The recombinant ST6GaINAc-I and ST6GaINAc-II showed similar substrate specificity toward glycoproteins and GaINAcalpha-O-Ser/Thr glycopeptides, such as glycopeptides derived from the MUC2 mucin and the HIVgp120. We also observed that the amino acid sequence of the acceptor glycopeptide contributes to the in vitro substrate specificity of both enzymes. We additionally established a gastric cell line, MKN45, stably transfected with the full length of either ST6GaINAc-I or ST6GaINAc-II and evaluated the carbohydrate antigens expression profile induced by each enzyme. MKN45 transfected with ST6GaINAc-I showed high expression of Sialyl-Tn, whereas MKN45 transfected with ST6GaINAc-II showed the biosynthesis of the Sialyl-6T structure [GaIbeta1-3 (Neu5Acalpha2-6)GaINAc-O-Ser/Thr]. In conclusion, although both enzymes show similar in vitro activities when Tn antigen alone is available, whenever both Tn and T antigens are present, ST6GaINAc-I acts preferentially on Tn antigen, whereas the ST6GaINAc-II acts preferentially on T antigen. Our results show that ST6GaINAc-I is the major Sialyl-Tn synthase and strongly support the hypothesis that the expression of the Sialyl-Tn antigen in cancer cells is due to ST6GaINAc-I activity.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 8