38 Mucins as markers of cell differentiation and neoplastic transformation

Abstract

Mucins are synthesized by glandular epithelia and are the major components of mucus. The cloning of cDNAs encoding human apomucins facilitates the analysis of their structural complexity and heterogeneity. Until now, 8 independent genes (MUC1-MUC7) have been identified which encode Ser/Thr-rich proteins with repetitive domains. Using these cDNAs, as well as anti-apomucin antibodies raised against a variety of immunogens (i.e. native and Deglycosylation mucins, synthetic peptides, fusion proteins), a considerable amount of information has been obtained regarding the pattern of expression of each gene in tissues. Each mucin gene has a distinct normal tissue distribution. Thus, MUC1 and MUC5B are expressed in a wide variety of normal epithelia, whereas MUC2 is mainly expressed in the intestine, MUC5AC in the respiratory tract and in the stomach, and MUC6 in the antrum. Multiple mucin genes can be expressed in a given tissue and at the single cell level, although in certain tissues a high degree of specialization is observed: in the stomach MUC5AC is present in the superficial epithelium whereas MUC6 is present in antral glands. In the stomach, apomucin expression correlates with Lewis antigen expression, although it is not clear whether the primary amino acid sequence of mucins contains instructive signals for glycosylation. Altered expression of mucin genes in pathologic states has now been demonstrated, in particular in cancer tissues. In colonic and gastric cancers, loss ofexpression of MUC2 and MUC5AC takes place, respectively. In contrast, MUC2, MUC4 and MUC5AC are aberrantlyexpressed in pancreas cancer tissues. In benign proliferative lesions of the colon and the pancreas, changes in the expression of mucin genes have also been demonstrated. Preliminary data suggest that the pattern of mucin gene expression in cancer tissues may be related to the biological behaviour, although more work is necessary in this area. Cultured cell lines have been used to study the regulation of mucingene expression in vitro facilitating the study of the biology of mucinproducingcells. In conclusion, it is now possible to establish the mucin phenotype oftumors at the molecular level. This information allows a better study ofthe alterations of cell differentiation occurring during neoplastic transformationas well as the role of mucins in tumor progression.