Expression of sialyl-Tn antigen in breast cancer cells transfected with the human CMP-Neu5Ac: GalNAc alpha2,6-sialyltransferase (ST6GalNac I) cDNA.
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 GalNAc alpha-O-Ser/Thr. This reaction is mainly catalyzed by a CMP-Neu5Ac GalNAc alpha2,6-sialyltransferase: ST6GalNAc I. In order to generate STn-positive breast cancer cells, we have cloned a cDNA encoding the full-length 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 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.
Julien
S
S
Unité de Glycobiologie Structurale et Fonctionnelle, UMR CNRS no 8576, Laboratoire de Chimie Biologique, Université des Sciences et Technologies de Lille, F-59655 Villeneuve d'Ascq, France.
Krzewinski-Recchi
M A
MA
Harduin-Lepers
A
A
Gouyer
V
V
Huet
G
G
Le Bourhis
X
X
Delannoy
P
P
D015295:Antigens, Tumor-Associated, Carbohydrate / Q000737:chemistry / Q000378:metabolism*; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000235:genetics / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D002465:Cell Movement; D003001:Cloning, Molecular; D003110:Colonic Neoplasms / Q000201:enzymology / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D005260:Female; D005700:Galactosyltransferases / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D008969:Molecular Sequence Data; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012799:Sialyltransferases / Q000235:genetics* / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured
D015295:Antigens, Tumor-Associated, Carbohydrate; D014408:Biomarkers, Tumor; D018076:DNA, Complementary; C040286:Tn antigen; C055491:sialosyl-Tn antigen; D005700:Galactosyltransferases; C076385:glycoprotein-N-acetylgalactosamine 3-beta-galactosyltransferase; D012799:Sialyltransferases; C038525:CMP-N-acetylneuraminate-alpha-N-acetylgalactosaminide alpha-2,6-sialyltransferase