Access to peptide regions of a surface mucin (MUC1) is reduced by sialic acids.
Mucinous glycoproteins are present on the surfaces of tumor cells. Knowledge of which parts of the mucin molecule are accessible targets for cells of the immune system is important in the development of successful therapeutic approaches. One breast (ZR-75-1), two colon (Colo 205 and SW1116), and three pancreas (Capan-2, HPAF and SW1990) cancer cell lines were examined. The reactivities of antibodies HMFG-2, specific for the tripeptide (DTR) in the 20 amino acid tandem repeat of MUC1, and SM-3 (PDTRP) were greatly enhanced by pre-treating cells with an inhibitor of O-glycosylation, benzyl-alpha-N-acetylgalactosamide. However, desialylation of cell surfaces with neuraminidase or pre-treatment with an inhibitor of carbohydrate processing, monensin, also greatly enhanced the reactivities of HMFG-2, SM-3 and HMFG-1 (PDTR). Thus, sialic acids on termini of neighboring oligosaccharides significantly limit access to the peptide region recognized by antibodies HMFG-1/2 and SM-3.
Ho
J J
JJ
Gastrointestinal Research Laboratory, Veterans Affairs Medical Center, San Francisco, CA 94121, USA.
Cheng
S
S
Kim
Y S
YS
D000595:Amino Acid Sequence; D000906:Antibodies; D001943:Breast Neoplasms; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D002460:Cell Line; D003110:Colonic Neoplasms; D000939:Epitopes / Q000032:analysis; D006031:Glycosylation; D006801:Humans; D007118:Immunoassay; D008562:Membrane Glycoproteins / Q000032:analysis / Q000737:chemistry* / Q000378:metabolism; D008969:Molecular Sequence Data; D008985:Monensin / Q000494:pharmacology; D018396:Mucin-1; D009077:Mucins / Q000032:analysis / Q000737:chemistry* / Q000378:metabolism; D009363:Neoplasm Proteins / Q000032:analysis / Q000737:chemistry*; D009439:Neuraminidase / Q000378:metabolism / Q000494:pharmacology; D010190:Pancreatic Neoplasms; D012794:Sialic Acids; D014407:Tumor Cells, Cultured
D000906:Antibodies; D000939:Epitopes; D008562:Membrane Glycoproteins; D018396:Mucin-1; D009077:Mucins; D009363:Neoplasm Proteins; D012794:Sialic Acids; D008985:Monensin; D009439:Neuraminidase