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Expression of Sialyl-Tn antigen in breast cancer cells transfected with the human CMP-Neu5Ac: GalNAc α2,6-sialyltransferase (ST6GalNAc I) cDNA

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Abstract

Sialyl-Tn antigen (STn) is a cancer associated carbohydrate antigen over-expressed in several cancers including breast cancer, and currently associated with more aggressive diseases and poor prognosis. However, the commonly used breast cancer cell lines (MDA-MB-231, T47-D and MCF7) do not express STn antigen. The key step in the biosynthesis of STn is the transfer of a sialic acid residue in α2,6-linkage to GalNAcα-O-Ser/Thr. This reaction is mainly catalyzed by a CMP-Neu5Ac GalNAc α2,6-sialyltransferase: ST6GalNAc I. In order to generate STn-positive breast cancer cells, we have cloned a cDNA encoding the full-lenght human ST6GalNAc I from HT-29-MTX cells. The stable transfection of MDA-MB-231 with an expression vector encoding ST6GalNAc I induces the expression of STn antigen at the cell surface. The expression of STn short cuts the initial O-glycosylation pattern of these cell lines, by competing with the Core-1 β1,3-galactosyltransferase, the first enzyme involved in the elongation of O-glycan chains. Moreover, we show that STn expression is associated with morphological changes, decreased growth and increased migration of MDA-MB-231 cells.

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Authors and Affiliations

  1. Unité de Glycobiologie Structurale et Fonctionnelle, UMR CNRS n°8576, Laboratoire de Chimie Biologique, Université des Sciences et Technologies de Lille, F-59655, Villeneuve d'Ascq, France

    Sylvain Julien, Marie-Ange Krzewinski-Recchi & Anne Harduin-Lepers

  2. Unité INSERM 560, Place de Verdun, 59045, Lille cedex, France

    Valérie Gouyer & Guillemette Huet

  3. Laboratoire de Biologie du Développement, UPRES EA 1033, Université des Sciences et Technologies de Lille, F-59655, Villeneuve d'Ascq, France

    Xuefen Le Bourhis

  4. Unité de Glycobiologie Structurale et Fonctionnelle, UMR CNRS n°8576, Laboratoire de Chimie Biologique, Université des Sciences et Technologies de Lille, F-59655, Villeneuve d'Ascq, France

    Philippe Delannoy

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  1. Sylvain Julien
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Julien, S., Krzewinski-Recchi, MA., Harduin-Lepers, A. et al. Expression of Sialyl-Tn antigen in breast cancer cells transfected with the human CMP-Neu5Ac: GalNAc α2,6-sialyltransferase (ST6GalNAc I) cDNA. Glycoconj J 18, 883–893 (2001). https://doi.org/10.1023/A:1022200525695

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