Structure and Biology of a Carcinoma-associated Mucin, MUC1

Abstract

Although mucins have been studied at the biochemical and biophysical level for some time, attempts to define their structures in detail were only partially successful because of their size and complexity. The advent of monoclonal antibodies reactive with these molecules introduced a new approach to structural studies by defining antigenic epitopes, by allowing purification of the mucin molecules by affinity chromatography, and by providing a means to clone genes coding for the core proteins. By their profile of reactivity with the normal and cancer-associated mucin in a particular tissue, the antibodies also defined a difference in the mucin derived from the two sources. It is now clear that this difference lies in the carbohydrate side chains, as the core proteins are identical. Because the mucins are tumor-associated antigens and the cancer mucins can express epitopes that are relatively tumor specific, this family of molecules is now being intensively studied. There is also considerable interest in elucidating the normal function of the mucin and in determining whether, through an altered structure, this function is subverted in malignancy. In the next few years we should expect that the structure of other mucins will be defined in the same detail as the product of the MUC1 gene. We should also expect to see the continued application of mucin-reactive antibodies in the clinic and the investigation of mucins as agents for immunotherapy of some cancers. As to the function(s) of these molecules, perhaps we will learn enough in the future to make a critical reappraisal of the name.

Pathogenesis of invasive micropapillary carcinoma: role of MUC1 glycoprotein

“…14 It is composed of a cytoplasmic tail of 69 aa and a large extracellular domain that consists of a variable number of tandem repeats rich in serine and threonine residues. 9,15,16 This domain undergoes specific O-glycosylation to generate a broad range of glycosylated variants of the MUC1 -molecule differing between various organ sites. 9,16 The physical and chemical properties of this extracellular domain-large size, rigidity, and negative charge-are believed to be responsible for the ability of MUC1 to maintain lumen integrity in normal glandular tissues.…”

Heat shock fusion protein induces both specific and nonspecific anti‐tumor immunity

“…MUC1 is a transmembrane glycoprotein expressed by normal epithelial cells and overexpressed by carcinomas of epithelial origin [1]. The extracellular domain of the MUC1 protein consists of variable numbers of tandem repeats (VNTR) [2].…”

Targeting of macrophage galactose‐type C‐type lectin (MGL) induces DC signaling and activation

“…The Tn-MUC1 glycoform represents one of the tumor-associated antigens (TAAs) studied as an MGL ligand. MUC1 is a transmembrane epithelial mucin made up of a repeated stretch of 20 amino acid tandem repeated (TR) sequence with several sites of attachment for O-linked glycans [19]. In tumors, MUC1 is overexpressed, aberrantly glycosylated, and shed in the tissue microenvironment.…”