MUC1 and cancer.
The MUC1 membrane mucin was first identified as the molecule recognised by mouse monoclonal antibodies directed to epithelial cells, and the cancers which develop from them. Cloning the gene showed that the extracellular domain is made up of highly conserved repeats of 20 amino acids, the actual number varying between 25 and 100 depending on the allele. Each tandem repeat contains five potential glycosylation sites, and between doublets of threonines and serines lies an immunodominant region which contains the epitopes recognised by most of the mouse monoclonal antibodies. The O-glycans added to the mucin produced by the normal breast are core 2 based and can be complex, while the O-glycans added to the breast cancer mucin are mainly core 1 based. This means that some core protein epitopes in the tandem repeat which are masked in the normal mucin are exposed in the cancer associated mucin. Since novel carbohydrate epitopes are also carried on the breast cancer mucin, the molecule is antigenically distinct from the normal breast mucin. (Changes in glycosylation in other epithelial cancers have been observed but are not so well documented.) Immune responses to MUC1 have been seen in breast and ovarian cancer patients and clinical studies have been initiated to evaluate the use of antibodies to MUC1 and of immunogens based on MUC1 for immunotherapy of these patients. The role of the carbohydrates in the immune response and in other interactions with the effector cells of the immune system is of particular interest and is discussed.
Taylor-Papadimitriou
J
J
Imperial Cancer Research Fund, Breast Cancer Biology Group, Guy's Hospital, London, UK.
Burchell
J
J
Miles
D W
DW
Dalziel
M
M
D000595:Amino Acid Sequence; D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism; D017321:Clinical Trials, Phase I as Topic; D003110:Colonic Neoplasms / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006023:Glycoproteins / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D008969:Molecular Sequence Data; D018396:Mucin-1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D009369:Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000628:therapy; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
D006023:Glycoproteins; C116055:MUC1 tandem repeat peptide; D018396:Mucin-1; D010446:Peptide Fragments