MUCINS IN CANCER: PROTECTION AND CONTROL OF THE CELL SURFACE

[john]

I though this was interesting because it mentioned tumor markers (CA19-9, CA125) It also mentioned ErbB-2 (HER2), which is a target for some lung cancers

MUCINS IN CANCER: PROTECTION AND CONTROL OF THE CELL SURFACE

Michael A. Hollingsworth & Benjamin J. Swanson about the authors

Preface

Mucins — large extracellular proteins that are heavily glycosylated with complex oligosaccharides — establish a selective molecular barrier at the epithelial surface and engage in morphogenetic signal transduction. Alterations in mucin expression or glycosylation accompany the development of cancer and influence cellular growth, differentiation, transformation, adhesion, invasion and immune surveillance. Mucins are used as diagnostic markers in cancer, and are under investigation as therapeutic targets for cancer.

Summary

The outermost area of a typical aerodigestive epithelial surface consists of secreted gel-forming mucins, and serves as a point of interface with air, food, enzymes, acid pH, salt, bacteria and viruses. The secreted mucin layer might also contact the cell surface through interactions with membrane-associated mucins or other cell-surface molecules.

Complex mucin gels have been shown to capture and hold biologically active molecules that might function as indicators of molecular or physical breach of the mucin layer and, following their release, might incite inflammatory, repair or healing processes.

Cell-surface-associated mucins are bound to cells by an integral transmembrane domain and have relatively short cytoplasmic tails that associate with cytoskeletal elements, cytosolic adaptor proteins and/or participate in signal transduction. Mucins might serve as cell-surface receptors and sensors, and conduct signals in response to external stimuli that lead to coordinated cellular responses that include proliferation, differentiation, apoptosis or secretion of specialized cellular products.

Cancer cells, especially adenocarcinomas, express aberrant forms or amounts of mucins. The expression of distinct oligosaccharide structures, together with differential glycosylation of mucin core proteins, confers on tumour cells an enormous range of potential ligands for interaction with other receptors at the cell surface.

Cancer cells might use mucins in much the same way as normal epithelia — for protection from adverse growth conditions and to control the local molecular microenvironment during invasion and metastasis.

Mucins are hypothesized to contribute to tumour invasion by simultaneously disrupting existing interactions between opposing cells (anti-adhesion) and establishing new ligands for interaction between the invading cell and the adjoining cells (adhesion).

Mucins could contribute to the regulation of differentiation and proliferation of tumour cells, through ligand–receptor interactions (for example, between MUC4 and ERBB2 (also known as HER2/neu) and morphogenetic signal transduction.

Two of the most widely used serum diagnostic assays for adenocarcinomas (CA19-9 and CA125) recognize epitopes that are found on mucins. Several immunologically based clinical-therapy trials target mucins that are expressed by adenocarcinomas, including monoclonal-antibody-based therapies and tumour

[Fay A.]

Darn those renegade goblet cells...