To put it simply, mucins are large extracellular glycoproteins and the main proteins found in mucus. Mucus is a thick, slimy substance secreted by epithelial cells to protect orifices, such as the nose, eyes, and urinary tract, from the entry of foreign particles and pathogens, and it is also secreted in the stomach and along other internal surfaces for lubrication and protection.
Mucin Composition and Function
Mucins are roughly 50% or more glycan by mass (highly glycosylated by sulfated polysaccharide, or sialic acid – known as sialomucins) and contain a mucin domain, which is rich in the amino acids threonine, serine, and proline. A characteristic of mucins are their ability to form gels, which is present in most metazoans, and what gives mucus its slimy, sticky texture.
Mucins occur in either secreted or membrane-bound forms. Secreted mucins, and other secreted glycoproteins, are processed by the Golgi apparatus within the epithelial cells and secreted at the apical surface of the cell from secretory vesicles. Membrane-bound mucins are thought to act as signaling molecules. One research group attempting to identify the specifics regarding mucins is the Mucin Biology Group at the University of Gothenburg in Sweden.
There are currently more than 20 human mucin genes that have been identified. The genes encoding mucin proteins are generally designated MUC (MUC1-MUC20) and have homologs in many species other than humans. However, some of the genes have been recategorized and renamed based on overlap with cancer-associated antigens.
Association with Disease
Abnormal mucin glycosylation can be a marker of neoplastic changes and used as tumor-specific antigens, particularly in pancreatic, breast, and ovarian cancers. In this context, underglycosylation of the mucin protein can cause normally hidden epitopes to be exposed, resulting in the development of a specific cytotoxic T cell population against the abnormal cells. Aberrant expression is also a mechanism found to affect certain diseases and disorders. The over-expression of MUC1 has been associated with colorectal cancer, and MUC1 and MUC4 have been associated with prostate cancer, likely because of their roles in signaling. Aberrant local MUC13 expression and mutant alleles have been associated with ovarian cancer and inflammatory bowel disease.
There are also variations of mucins found to correlate with cancers, such as breast cancer mucin (BCM), mucin-like cancer-associated antigens (CA, encoded by some MUC genes), small intestine mucin antigen (SIMA), and large intestine mucin antigen (LIMA). The intestinal mucin antigens have also been associated with inflammatory diseases of the bowel, such as ulcerative colitis. Research on the exact roles and mechanism of mucins in disease processes is ongoing and advanced greatly over the last 20-25 years.
