Association of sialyl-Lewis(a) and sialyl-Lewis(x) with MUC-1 apomucin ina pancreatic cancer cell line.
We have shown previously that the mucins of the human pancreatic cancer cell line, SW1990, have both sialyl-Lewis(a) and sialyl-Lewis(x) carbohydrate ligands that are implicated in tumor cell metastasis. In the present study, we undertook to identify the protein core of these mucins. SW1990 mucins that carry sialyl-Lewis(a) and sialyl-Lewis(x) bound to the MUC1 peptide-specific mAb 139H2. Removal of most of the sialic acids from SW1990 mucins by neuraminidase greatly enhanced binding of two other MUC1 peptide specific antibodies, HMFG-2 and SM-3. After removal of sialic acids, most of the mucins rich in sialyl-Lewis(a) and sialyl-Lewis(x) oligosaccharides no longer bound to a DEAE-cellulose column at pH 8.0. These results indicate that at least part of the sialyl-Lewis(a) and sialyl-Lewis(x) in SW1990 cells is associated with the MUC1 polypeptide. Moreover, sialic acids play an important role in determining the net negative charge of sialyl-Lewis(a) and sialyl-Lewis(x) rich mucins and in obscuring MUC1 peptide regions.
Ho
J J
JJ
Gastrointestinal Research Laboratory, Veterans Affairs Medical Center, San Francisco, CA 94121, USA.
Siddiki
B
B
Kim
Y S
YS
D000595:Amino Acid Sequence; D000912:Antibodies, Neoplasm / Q000276:immunology; D000918:Antibody Specificity; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000737:chemistry / Q000378:metabolism*; D018395:CA-19-9 Antigen; D018270:Carcinoma, Ductal, Breast / Q000276:immunology / Q000378:metabolism*; D018604:Epitope Mapping; D005732:Gangliosides / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D018396:Mucin-1; D009077:Mucins / Q000737:chemistry / Q000378:metabolism*; D009439:Neuraminidase / Q000494:pharmacology; D010190:Pancreatic Neoplasms / Q000276:immunology / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D000080506:Sialyl Lewis X Antigen; D014407:Tumor Cells, Cultured
D000912:Antibodies, Neoplasm; D015295:Antigens, Tumor-Associated, Carbohydrate; D018395:CA-19-9 Antigen; D005732:Gangliosides; D008562:Membrane Glycoproteins; D018396:Mucin-1; D009077:Mucins; D010455:Peptides; D000080506:Sialyl Lewis X Antigen; C094688:sialyl Lewis(x) ganglioside; C064564:sialyl Le(a) ganglioside; D009439:Neuraminidase