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Stable expression of sialyl-Tn antigen in T47-D cells induces a decrease of cell adhesion and an increase of cell migration

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Summary

Sialyl-Tn is a carbohydrate antigen overexpressed in several epithelial cancers including breast cancer, and usually associated with poor prognosis. Sialyl-Tn is synthesized by a CMP-Neu5Ac: GalNAc α2,6-sialyltransferase: ST6GalNAc I, which catalyzes the transfer of a sialic acid residue in α2,6-linkage to the GalNAcα1-O-Ser/Thr structure. The resulting disaccharide (Neu5Acα2-6GalNAcα1-O-Ser/Thr) cannot be further elongated and sialyl-Tn expression results therefore in a shortening of the O-glycan chains. However, usual breast cancer cell lines express neither ST6GalNAc I nor sialyl-Tn antigen. We have previously shown that stable transfection of MDA-MB-231 cells with the hST6GalNAc I cDNA induces the sialyl-Tn antigen expression at the cell surface and leads to a decreased cell growth and an increased cell migration. We describe herein the generation of new T47-D clones expressing sialyl-Tn antigen after hST6GalNAc I cDNA stable transfection. sialyl-Tn antigen is carried by several high molecular weight membrane bound O-glycoproteins, including MUC1. We show that sialyl-Tn expression induces a decrease of cell growth and adhesion, and an increase of cell migration in sialyl-Tn positive clones compared to mock transfected cells. These observations show that the alteration of the O-glycans pattern is sufficient to modify the biological features of cancer cells. These T47-D sialyl-Tn expressing clones might allow further in vivo investigation to determine precisely the impact of such O-glycosylation modifications on breast cancer development.

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Abbreviations

Core1β3GalT:

UDP-Gal

GalNAc β1,3:

galactosyltransferase (EC 2.4.1.122)

ECM:

extracellular matrix

mAb:

monoclonal antibody

NBT:

nitroblue tetrazolium

ST6GalNAc I:

CMP-Neu5Ac

R-GalNAcα1:

O-Ser/Thr α2,6-sialyltransferase (EC 2.4.99.3)

STn:

sialyl-Tn antigen

Tn antigen:

Thomsen-nouveau antigen

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Correspondence to Philippe Delannoy.

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Julien, S., Lagadec, C., Krzewinski-Recchi, MA. et al. Stable expression of sialyl-Tn antigen in T47-D cells induces a decrease of cell adhesion and an increase of cell migration. Breast Cancer Res Treat 90, 77–84 (2005). https://doi.org/10.1007/s10549-004-3137-3

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