Multiple roles of mucins in pancreatic cancer, a lethal and challenging malignancy

Abstract

Mucins are members of an expanding family of large multifunctional glycoproteins. Pancreatic mucins have important biological functions, including the protection, lubrication, and moisturisation of the surfaces of epithelial tissues lining ductal structures within the pancreas. Several lines of evidence support the notion that deregulated mucin production is a hallmark of inflammatory and neoplastic disorders of the pancreas. Herein, we discuss the factors that contribute to the lethality of pancreatic cancer as well as the key role played by mucins, particularly MUC1 and MUC4, in the development and progression of the disease. Aspects pertaining to the aberrant expression and glycosylation of mucins are discussed, with special emphasis on their potential impact on the design and implementation of adequate diagnostic and therapeutic strategies for combating this lethal malignancy.

Mucin impedes cytotoxic effect of 5-FU against growth of human pancreatic cancer cells: overcoming cellular barriers for therapeutic gain

“…In several studies we used a FITCconjugated CD227 antibody to probe the existence of a single mucin variety, MUC1. We note that other membrane-bound mucins such as MUC3, MUC4, MUC12, MUC16 and MUC17 are also present (Hollingsworth and Swanson, 2004;Moniaux et al, 2004); relative contribution to the functional mucin barrier effect is probably determined by their relative abundance and extended extracellular domain sequence.…”

Posttranslational Protein Modifications

“…The carbohydrate content of the secreted mucins represents about 25% of their total mass conferring them with hydrodynamic properties believed to impart lubrication and protection at the luminal cell surface. In several types of cancer, overexpression of mucins has been noted; these mucins typically display abnormal or incomplete glycosylation (39,40). The ovarian carcinoma biomarker CA125 is a mucin where only relatively recently has the repertoire of its diverse oligosaccharide structures been elucidated (41).…”

Aberrant expression of MUC4 in ovarian carcinoma: diagnostic significance alone and in combination with MUC1 and MUC16 (CA125)

“…10,13,14 However, mucins are also believed to play an important role in the pathogenesis of benign and malignant diseases of secretory epithelial cells. 10,11,15 An aberrant expression of mucins has been reported in a variety of carcinomas. CA125, a tumor biomarker being used in clinics for the diagnosis of EOC, is actually a mucin (MUC16).…”