Transmembrane mucins as novel therapeutic targets

Abstract

Membrane-tethered mucin glycoproteins are abundantly expressed at the apical surfaces of simple epithelia, where they play important roles in lubricating and protecting tissues from pathogens and enzymatic attack. Notable examples of these mucins are MUC1, MUC4 and MUC16 (also known as cancer antigen 125). In adenocarcinomas, apical mucin restriction is lost and overall expression is often highly increased. High-level mucin expression protects tumors from killing by the host immune system, as well as by chemotherapeutic agents, and affords protection from apoptosis. Mucin expression can increase as the result of gene duplication and/or in response to hormones, cytokines and growth factors prevalent in the tumor milieu. Rises in the normally low levels of mucin fragments in serum have been used as markers of disease, such as tumor burden, for many years. Currently, several approaches are being examined that target mucins for immunization or nanomedicine using mucin-specific antibodies.

Keywords::

• cytokines
• MUC1
• MUC16
• MUC4
• nanomedicine
• steroid hormones

Acknowledgements

The authors thank Mary C Farach-Carson and members of the Carson and Farach-Carson laboratories for many helpful discussions. We are deeply appreciative of the excellent secretarial assistance of Sharron Kingston.

Financial & competing interests disclosure

The authors were supported by NIH grant R01HD029963 (to Daniel D Carson), NIH grant P50CA098258 NCI Uterine SPORE Pilot Project (to Daniel D Carson) and NIH grant U54 CA151668 Pilot Project (to Pamela Constantinou). The authors have no other relevant affiliations or financial in involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.