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  • Review Article
  • Published:

Mucins in pancreatic cancer and its microenvironment

Nature Reviews Gastroenterology & Hepatology volume 10, pages 607–620 (2013)Cite this article

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Abstract

Pancreatic cancer remains a lethal malignancy with poor prognosis owing to therapeutic resistance, frequent recurrence and the absence of treatment strategies that specifically target the tumour and its supporting stroma. Deregulated cell-surface proteins drive neoplastic transformations and are envisioned to mediate crosstalk between the tumour and its microenvironment. Emerging studies have elaborated on the role of mucins in diverse biological functions, including enhanced tumorigenicity, invasiveness, metastasis and drug resistance through their characteristic O-linked and N-linked oligosaccharides (glycans), extended structures and unique domains. Multiple mucin domains differentially interact and regulate different components of the tumour microenvironment. This Review discusses: the expression pattern of various mucins in the pancreas under healthy, inflammatory, and cancerous conditions; the context-dependent attributes of mucins that differ under healthy and pathological conditions; the contribution of the tumour microenvironment in pancreatic cancer development and/or progression; diagnostic and/or prognostic efficacy of mucins; and mucin-based therapeutic strategies. Overall, this information should help to delineate the intricacies of pancreatic cancer by exploring the family of mucins, which, through various mechanisms in both tumour cells and the microenvironment, worsen disease outcome.

Key Points

  • Mucins, by virtue of their extended ectodomain, variety of domains and varied degree of glycosylation, act as multifaceted glycoproteins that have evolved convergently to protect the exposed surfaces of organisms

  • Pancreatic cancer is characterized by the aberrant expression of both transmembrane and secretory mucins

  • De novo expression of MUC4, MUC5AC, and MUC16 is observed in pancreatic cancer as early as pancreatic intraepithelial neoplasia and expression increases gradually with disease progression and subsequent metastasis

  • Altered attributes of mucins are used by tumour cells to facilitate their growth, proliferation, interaction with the extracellular matrix or stromal cells and detachment from the primary tumour for invasion and metastasis

  • CA19-9, the FDA-approved prognostic marker for pancreatic cancer, is a carbohydrate antigen (sialyl Lewisa) present on the surface of MUC1, MUC16 and MUC5AC; MUC1-based therapies are in preclinical and clinical trials

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Figure 1: Domain structure of transmembrane and secretory mucins.
Figure 2: Mucins in transition from normal to malignant cells.
Figure 3: Antigenic and differently expressed O-glycans of pancreatic cancer.
Figure 4: Tumour cells crosstalk with stromal cells via mucins.
Figure 5: Mucins as therapeutic targets.

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Acknowledgements

The authors on this work are supported, in part, by grants from the NIH (TMEN U54 CA163120, EDRN UO1 CA111294, SPORE P50 CA127297, RO1 CA131944, RO1 CA133774, RO1 CA78590 and RO3 CA167342).

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  1. Department of Biochemistry and Molecular Biology, 985870 Nebraska Medical Centre, Omaha, 68198-5870, NE, USA

    Sukhwinder Kaur, Sushil Kumar, Navneet Momi & Surinder K. Batra

  2. Department of Surgery, University of Nebraska Medical Centre, 985870 Nebraska Medical Centre, Omaha, 68198-5870, NE, USA

    Aaron R. Sasson

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S. Kaur, S. Kumar, N. Momi and S. K. Batra contributed to all aspects of producing this article. A. R. Sasson substantially contributed to the discussion of content and reviewed and/or edited the article before submission.

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Correspondence to Surinder K. Batra.

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Kaur, S., Kumar, S., Momi, N. et al. Mucins in pancreatic cancer and its microenvironment. Nat Rev Gastroenterol Hepatol 10, 607–620 (2013). https://doi.org/10.1038/nrgastro.2013.120

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