Modification of blood group A expression in human pancreatic tumor cell lines by inhibitors of N-glycan processing.

Abstract

Pancreatic adenocarcinomas induced in Syrian hamsters by N-nitrosobis (2-oxopropyl)amine (BOP) treatment express blood group A (BGA) antigen, which was previously shown by this lab to be expressed on multiantennary asparagine (Asn)-linked glycans attached to membrane glycoproteins. To determine if a similar expression pattern was found in humans, three human pancreatic ductal adenocarcinoma cell lines (CD18, CD11, and Capan 1) from individuals of blood type A were analyzed and shown to express BGA antigen on membrane glycoproteins similar in molecular mass to those found in hamster tumor cells. The BGA antigen was located on Asn-linked oligosaccharides in all three human cell lines, as indicated by loss of activity after peptide:N-glycosidase F (PNGase F) treatment. Also, as shown previously in hamster pancreatic tumor cells, BGA expression at the surface of the human cell lines was blocked by growth of the cells in media containing deoxymannojirimycin (dMM), an inhibitor of mannosidase I. These results demonstrate that the BGA antigen is on Asn-linked glycans in human pancreatic adenocarcinoma cells and that these glycoproteins are processed similarly to the BGA glycoproteins in hamster pancreatic adenocarcinoma.