Distinct sub-populations of carcinoma-associated MUC1 mucins as detected by the monoclonal antibody 9H8 and antibodies against the sialyl-Lewis a and sialyl-Lewis x epitopes in the circulation of breast-cancer patients.
The cancer-associated epitope defined by the monoclonal antibody (MAb) 9H8 was shown to be closely related to the T antigen (Thomsen-Friedenreich antigen) by its sensitivity to 0-glycanase treatment of a mucin glycopeptide known to express this epitope. The reactivity with this glycopeptide increased upon neuraminiclase treatment, and among several MAbs tested for ability to block binding of the 9H8 antibody, the one specific for the T antigen was the most efficient. Out of 41 serum samples from breast-cancer patients, 11 showed elevated levels of the 9H8 epitope, and several sera also showed elevated levels of the cancer-associated carbohydrate epitopes sialyl-Lewis a and sialyl-Lewis x. By the use of antibodies specific for the MUC1 apoprotein (Ma552 and HMFG-2) it could be shown that these epitopes were attached to the MUC1 apoprotein in at least 4 of the cases. By combining antibodies specific to 9H8, sialyl-Lewis a and sialyl-Lewis x in catcher and tracer positions in several types of immunofluorometric assays, it was shown that the 9H8 epitope was rarely co-expressed with sialyl-Lewis a or sialyl-Lewis x epitopes an the same molecule, though all were expressed on MUC1 mucins. In fact, they can be considered as mutually exclusive epitopes, suggesting that these sera contained different populations of MUC1 mucins distinguishable by different sets of oligosaccharides. The existence of mutually exclusive carbohydrate epitopes on different MUC1 mucins in one and the same patient should be taken into account when designing immunoassays exploiting MUC1-reactive antibodies.
Sikut
R
R
Institute of Molecular and Cell Biology, University of Tartu, Estonia.
Zhang
K
K
Baeckström
D
D
Hansson
G C
GC
D000906:Antibodies / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000276:immunology*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000097:blood* / Q000276:immunology; D018395:CA-19-9 Antigen; D002240:Carbohydrate Sequence; D004586:Electrophoresis; D000939:Epitopes / Q000276:immunology*; D005260:Female; D015200:Fluoroimmunoassay; D005732:Gangliosides / Q000097:blood / Q000276:immunology*; D006801:Humans; D008969:Molecular Sequence Data; D018396:Mucin-1 / Q000097:blood*; D000080506:Sialyl Lewis X Antigen
D000906:Antibodies; D000911:Antibodies, Monoclonal; D018395:CA-19-9 Antigen; D000939:Epitopes; D005732:Gangliosides; D018396:Mucin-1; D000080506:Sialyl Lewis X Antigen; C094688:sialyl Lewis(x) ganglioside; C025991:Thomsen-Friedenreich antibodies; C064564:sialyl Le(a) ganglioside