Development and characterization of breast cancer reactive monoclonal antibodies directed to the core protein of the human milk mucin.
A mucin molecule, which has a molecular weight of greater than 400,000 and which carries tumor associated epitopes recognized by monoclonal antibodies HMFG-1 and HMFG-2, has been purified from human skimmed milk by affinity chromatography followed by passage through a size exclusion column. While treatment of the mucin with hydrogen fluoride for 1 h at 4 degrees C removed the peripheral oligosaccharides, treatment with HF for 3 h at room temperature removed all of its lectin binding ability and revealed a dominant polypeptide of about 68,000. This appears to be the size of the mucin core protein. Monoclonal antibodies have been developed that react with the stripped and partially stripped molecule but not with the intact mucin. From the initial screening on histological sections one of these antibodies, SM-3, reacts with 91% of breast carcinomas but shows little or no reactivity on benign mammary tumors, normal resting, pregnant, or lactating breast. It appears that this monoclonal antibody is reacting with an epitope that is usually masked by oligosaccharide moieties in normal cells but which is exposed, perhaps due to aberrant glycosylation, in malignant cells.
D000596:Amino Acids / Q000032:analysis; D000911:Antibodies, Monoclonal; D001940:Breast / Q000032:analysis; D001943:Breast Neoplasms / Q000276:immunology*; D002846:Chromatography, Affinity; D000939:Epitopes / Q000032:analysis; D005260:Female; D006801:Humans; D006858:Hydrofluoric Acid / Q000494:pharmacology; D007163:Immunosorbent Techniques; D007774:Lactation; D008895:Milk, Human / Q000032:analysis; D008970:Molecular Weight; D009077:Mucins / Q000276:immunology*; D011247:Pregnancy
D000596:Amino Acids; D000911:Antibodies, Monoclonal; D000939:Epitopes; D009077:Mucins; D006858:Hydrofluoric Acid