Immunochemical studies of mucin-type glycoproteins

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To reveal the characteristic structures of mucins, mucin-specific monoclonal antibodies, MSW 113, MLS 102 and MLS 128, have been established. Using MSW 113, as an immunoaffinity agent, oligosaccharides have been isolated from human colostrum, all of which have the sialyl-Le^a determinant in linear and branched structures. Some of the oligosaccharides have the sialyl-Le^x determinant in addition to the sialyl-Le^a in the same molecule. These indicate that MSW 113 have a broad binding specificity.MSW 113 is in fact superior to NS 19-9, recognizing sialyl-Le^a structure specifically, in reacting with oligosaccharides having a variety of structures, which made MSW 113 a useful reagent to detect cancer antigens in sera of patients.Epitopes for MLS 102 and MLS 128, respectively, have been determined. MLS 102 is an anti-sialyl Tn antibody. From ovine submaxillary mucin (OSM), glycopeptides with a cluster structure, composed of Sia-GalNAc-Ser/Thr, have been isolated. After the removel of sialic acid, the glycopeptides turned out to be the epitope for MLS 128, an anti-Tn antibody. The cluster structure composed of three or four consecutive sequences of GalNAc-Ser/Thr was initially found in OSM,but similar clusters have then been found in Tn-glycophorin A from Tn erythrocyte and leukosialin from a T-lymphoid cell, Jurkat.Sialyl Tn and Tn antigens have been regarded as tumor marker. In fact, MLS 102 and MLS 128 are effective in staining histochemically cancer tissues, thus being potentially candidates for in vivo imaging agents for cancer patients.Mucins were isolated from cancer cells and pleural fluids from cancer patients and their carbohydrate moieties were analyzed. Like OSM,these mucins express at least both sialyl Tn and Tn antigens. The factors which determine the co-expression of these two antigens remain unknown, since the co-expression occurs in the circumstance where sugar transferases including sialyl transferase occur.