[New mucin core protein genes and their clinical application]

Recent molecular biological approach has revealed the primary structure of some mucin core proteins. Most prominent characteristic is tandemly repeated sequences. cDNA cloning of 8 kinds of mucin core proteins, MUC1-7, have thus been performed. Among them, the entire structure was revealed on MUC1,2 and 7. MUC1 is a type I transmembrane protein with a large number of tandem repeat consisting of 20 amino acids. We have found that mouse MoAb MUSE11 against adenocarcinoma, which detects circulating MUC1 in patients with gastrointestinal and pancreatic cancers, recognizes part of the tandem repeat of MUC1 using synthetic peptides. We have transfected MUC1 cDNA to some cell lines, and they indicated that cell-cell and cell-matrix adhesion, growth rate and reactivity with growth factor were suppressed. To date, some of the MoAbs to adenocarcinoma have been shown to react with PDTRP sequence in the tandem repeat of MUC1 (MUC1 epitope), suggesting that MUC1 epitope could be highly immunogenic in human. Recently, cytotoxic T-cells against MUC1 epitope were established from breast and pancreas cancer patients. We also induce those T-cells from the patient with multiple myeloma. Interestingly, CTL functions in an HLA-unrestricted manner, and may be of use an adoptive immunotherapy. MUC2, a large secretory type mucin, cysteine-rich subdomains located both upstream and downstream of its central repetitive region, and these subdomains have sequence similarity with von Willebrand factor. We have shown that anti MUC2 core-protein MoAb CCP58 reacts intestinal metaplasia and cancer in stomach, but not normal gastric mucous membrane. Recently we established a new monoclonal antibody against purified deglycosylated gastric mucin. This antigen was expressed in the deep portion of metaplastic glands and cancers in the stomach. Two cDNA clones coding for this antigenic molecule were obtained.