Expression of core 2 beta-1,6-N-acetylglucosaminyltransferase in a human pancreatic cancer cell line results in altered expression of MUC1 tumor-associated epitopes

Many tumor-associated epitopes possess carbohydrate as a key component, and thus changes in the activity of glycosyltransferases could play a role in generating these epitopes, In this report we describe the stable transfecti on of a human pancreatic adenocarcinoma cell line, Panc1-MUC1, with the cDN A for mucin core 2 GlcNAc-transferase (C2GnT), which creates the core 2 bet a-1,6 branch in mucin-type glycans, These cells lack endogenous C2GnT activ ity but express a recombinant human MUC1 cDNA, C2GnT-transfected clones exp ressing different levels of C2GnT were characterized using monoclonal antib odies CC49, CSLEX-1, and SM-3, which recognize tumor-associated epitopes, I ncreased C2GnT expression led to greatly diminished expression of the CC49 epitope, which we identified as NeuAc alpha 2,6-(Ga1 beta 1,3)GalNAc alpha- Ser/Thr in the Panc1-MUC1 cells. This was accompanied by the emergence of t he CSLEX-1 epitope, sialyl Lewis x (NeuAc alpha 2,3Gal beta 1,4(Fuc alpha 1 ,3)GlcNAc-R), an important selectin ligand, Despite this, however, the C2Gn T transfectants could not bind to selectins, Increased C2GnT expression als o led to masking of the SM-3 peptide epitope, which persisted after the rem oval of sialic acid, further suggesting greater complexity of the core a-as sociated O-glycans on MUC1. The results of this study suggest that C2GnT co uld play a regulatory role in the expression of certain tumor-associated ep itopes.