MUC1 as a human tumor marker

Abstract

MUC1 mucin serves as a tumor-associated antigen in various carcinomas. We have reported the expression of MUC1 in multiple myeloma (MM) cells and the establishment of an HLA-unrestricted cytotoxic T lymphocyte (CTL) that recognized MUC1 from peripheral lymphocytes in a patient with MM. In this study, we successfully induced MUC1-specific CTLs from bone marrow cells in two MM patients. Both CTLs lysed MUC1-positive cell lines with different kinds of HLA, and the cytotoxicity was inhibited by anti-CD3, anti-αβ T cell receptor and anti-MUC1 monoclonal antibodies. The treatment with O-glycosylation inhibitor augmented the cytotoxicity of the CTLs. These data showed that HLA-unrestricted CTLs that recognize the underglycosylated form of MUC1 could be induced from MM patients. MUC1 is also an important factor in cancer metastasis. We previously reported that MUC1 mucin has anti-adhesion effects that contribute to the separation of tumor cells from the primary site. We next investigated the involvement of MUC1 in tumor invasion that is a second step of metastasis. MUC1-transfectants transplanted subcutaneously into nude mice invaded the muscular layer. The treatment with O-glycosylation inhibitor abolished these effects of MUC1. Our data indicated that MUC1 mucin increases the invasive ability of tumor cells, while O-glycan plays an essential role.