Journal
GLYCOCONJUGATE JOURNAL
Volume 18, Issue 11-12, Pages 883-893Publisher
KLUWER ACADEMIC PUBL
DOI: 10.1023/A:1022200525695
Keywords
breast cancer; sialyl-Tn; ST6GalNAc 1; O-glycosylation
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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 alpha2,6-linkage to GalNAcalpha-O-Ser/Thr. This reaction is mainly catalyzed by a CMP-Neu5Ac GalNAc alpha2,6-sialyltransferase: ST6GalNAc 1. In order to generate STn-positive breast cancer cells, we have cloned a cDNA encoding the full-lenght human ST6GaINAc I from HT-29-MTX cells. The stable transfection of MDA-MB-231 with an expression vector encoding ST6GaINAc 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 beta1,3-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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