MUC1 and the immunobiology of cancer

Abstract

The membrane epithelial mucin MUC1 is expressed at the luminal surface of most simple epithelial cells, but expression is greatly increased at lactation and in most breast carcinomas. The increase in level of expression of MUC1 in breast cancer is accompanied by changes in the profile of glycosyl transferases involved in the synthesis of the O-glycans attached to the MUC1 core protein. The cancer-associated mucin is therefore structurally different from the normal mucin, and expresses novel B cell epitopes. MUC1 antibodies are used for in vivo targeting of breast and ovarian tumors, and there is considerable interest in MUC1 as a possible target antigen for the immunotherapy of breast cancer. The different glycoforms can affect cell interactions differently, depending on whether specific interactions with lectins occur. In the absence of such lectin interactions, the long sialylated and negatively charged molecule can inhibit intercellular interactions between other cell surface molecules. The potential role of the different components of the immune system in MUC1 responses are discussed within the framework of how to develop logical strategies for designing clinical studies.