Mucin glycoproteins in neoplasia.
Mucins are high molecular weight glycoproteins that are heavily glycosylated with many oligosaccharide side chains linked O-glycosidically to the protein backbone. With the recent application of molecular biological methods, the structures of apomucins and regulation of mucin genes are beginning to be understood. At least nine human mucin genes have been identified to date. Although a complete protein sequence is known for only three human mucins (MUC1, MUC2, and MUC7), common motifs have been identified in many mucins. The pattern of tissue and cell-specific expression of these mucin genes are emerging, suggesting a distinct role for each member of this diverse mucin gene family. In epithelial cancers, many of the phenotypic markers for pre-malignant and malignant cells have been found on the carbohydrate and peptide moieties of mucin glycoproteins. The expression of carbohydrate antigens appears to be due to modification of peripheral carbohydrate structures and the exposure of inner core region carbohydrates. The expression of some of the sialylated carbohydrate antigens appears to correlate with poor prognosis and increased metastatic potential in some cancers. The exposure of peptide backbone structures of mucin glycoproteins in malignancies appears to be due to abnormal glycosylation during biosynthesis. Dysregulation of tissue and cell-specific expression of mucin genes also occurs in epithelial cancers. At present, the role of mucin glycoproteins in various stages of epithelial cell carcinogenesis (including the preneoplastic state and metastasis), in cancer diagnosis and immunotherapy is under investigation.
GI Research Lab, VA Medical Center, San Francisco, CA 94121, USA.
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Kim
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Gum
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Brockhausen
D000595:Amino Acid Sequence; D000941:Antigens / Q000737:chemistry / Q000276:immunology; D002240:Carbohydrate Sequence; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009077:Mucins / Q000737:chemistry*; D009369:Neoplasms / Q000737:chemistry*; D009844:Oligosaccharides / Q000737:chemistry / Q000276:immunology; D010455:Peptides / Q000737:chemistry; D012091:Repetitive Sequences, Nucleic Acid
D000941:Antigens; D009077:Mucins; D009844:Oligosaccharides; D010455:Peptides