A core protein epitope of the polymorphic epithelial mucin detected by the monoclonal antibody SM‐3 is selectively exposed in a range of primary carcinomas

Abstract

The monoclonal antibody (MAb) SM-3, which was raised to chemically deglycosylated milk mucin, reacts with an epitope present on the core protein of this mucin which we have referred to as PEM (polymorphic epithelial mucin). Although this mucin is abundantly expressed by both the lactating breast and breast carcinomas, the antibody SM-3 shows very little or no reactivity on the former but does react with 92% of breast carcinomas. Furthermore, SM-3 stains primary carcinomas of the lung, colon and ovary, but on the corresponding normal tissue the epitope is expressed at a much reduced level or not at all. These results indicate that an epitope masked in the normal mucin is exposed in the mucin produced by tumour cells, perhaps due to aberrant glycosylation. An extensive immunohistochemical study of other normal tissues reveals that the majority show only weak focal staining with SM-3 or none at all, the distal tubules and collecting ducts of the kidney, and sebaceous glands being the only normal tissues studied to show homogeneously positive staining.

MUC1 expression in human prostate cancer cell lines and primary tumors

“…2,4,[8][9][10][11][12] In particular, the extracellular domain of MUC1 facilitates cancer progression. It also can promote adhesion due to the presentation of carbohydrate ligands that bind to selectin-like molecules on endothelial cells.…”

“…MUC1 expression in tumors is greatly increased and accompanied by altered glycosylation and aberrant expression patterns that become more diffuse when compared to the normal apically restricted pattern. [9][10][11][12] Moreover, MUC1 is proposed to help tumor cells evade host defenses by attenuating immune responses and to promote metastasis through a loss of cell-cell and cell-extracellular matrix (ECM) contact (reviewed in Taylor-Papadimitriou et al 4 ).…”

Recombinant MUC1 mucin with a breast cancer-like O-glycosylation produced in large amounts in Chinese-hamster ovary cells

“…MUC1 was first identified as an epithelial cell protein [1], but has recently also been found at low levels on cells of haematopoietic origin [2][3][4]. The expression of MUC1 is elevated in many forms of epithelial cancers, including those of the breast, lung, cervix, colon and pancreas [5,6].…”

Responses of human T cells to peptides flanking the tandem repeat and overlapping the signal sequence of MUC1

“…1,2 Its expression is increased in many epithelial malignancies, notably breast, pancreatic and ovarian cancers. 3,4 Its extracellular domain consists largely of TR sequences of 20 amino acids, 1 each of which contains 5 potential O-glycosylation sites; and the glycoforms produced by cancer cells can differ from those expressed by normal tissues. 5 There have been reports of humoral and cellular immune responses to MUC1 in multiparous women and in cancer patients, 6 with the presence of a humoral response reportedly being a good prognostic factor for outcome in breast cancer patients.…”