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Review
. 2019 Mar 14;20(6):1288.
doi: 10.3390/ijms20061288.

Mucins: the Old, the New and the Promising Factors in Hepatobiliary Carcinogenesis

Aldona Kasprzak  1 , Agnieszka Adamek  2
Affiliations
Review

Mucins: the Old, the New and the Promising Factors in Hepatobiliary Carcinogenesis

Aldona Kasprzak et al. Int J Mol Sci. .

Abstract

Mucins are large O-glycoproteins with high carbohydrate content and marked diversity in both the apoprotein and the oligosaccharide moieties. All three mucin types, trans-membrane (e.g., MUC1, MUC4, MUC16), secreted (gel-forming) (e.g., MUC2, MUC5AC, MUC6) and soluble (non-gel-forming) (e.g., MUC7, MUC8, MUC9, MUC20), are critical in maintaining cellular functions, particularly those of epithelial surfaces. Their aberrant expression and/or altered subcellular localization is a factor of tumour growth and apoptosis induced by oxidative stress and several anti-cancer agents. Abnormal expression of mucins was observed in human carcinomas that arise in various gastrointestinal organs. It was widely believed that hepatocellular carcinoma (HCC) does not produce mucins, whereas cholangiocarcinoma (CC) or combined HCC-CC may produce these glycoproteins. However, a growing number of reports shows that mucins can be produced by HCC cells that do not exhibit or are yet to undergo, morphological differentiation to biliary phenotypes. Evaluation of mucin expression levels in precursors and early lesions of CC, as well as other types of primary liver cancer (PLC), conducted in in vitro and in vivo models, allowed to discover the mechanisms of their action, as well as their participation in the most important signalling pathways of liver cystogenesis and carcinogenesis. Analysis of mucin expression in PLC has both basic research and clinical value. Mucins may act as oncogenes and tumour-promoting (e.g., MUC1, MUC13), and/or tumour-suppressing factors (e.g., MUC15). Given their role in promoting PLC progression, both classic (MUC1, MUC2, MUC4, MUC5AC, MUC6) and currently tested mucins (e.g., MUC13, MUC15, MUC16) have been proposed to be important diagnostic and prognostic markers. The purpose of this review was to summarize and update the role of classic and currently tested mucins in pathogenesis of PLC, with explaining the mechanisms of their action in HCC carcinogenesis. It also focuses on determination of the diagnostic and prognostic role of these glycoproteins in PLC, especially focusing on HCC, CC and other hepatic tumours with- and without biliary differentiation.

Keywords: hepatobiliary carcinogenesis; liver cancer immunophenotype; mucins; mucins as oncogenes; primary liver cancer; tissue expression.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Proposed model of two trans-membrane mucins (MUC1, MUC13) action in promoting hepatocellular carcinoma (HCC) growth, tumour progression and metastasis, as well as the role of MUC15 in inhibition of tumour growth and metastases (with own modifications) [38,39,40,41,42,53,56]. The signalling pathways downstream of the activated Wnt/β-catenin, MAPK with JNK/AP-1, TGF-β with JNK/pSmad3L/c-Myc and JAK2/STAT3 are known to stimulate cancer cell proliferation, survival, migration, invasion and inhibit cell apoptosis; whereas TβRI/pSmad3C/p21WAF1 is tumour suppressive signalling. The inhibitory effect of MUC15 on PI3K/AKT signalling pathway is linked to negative regulation of metastasis and local growth of HCC cells. Legend: ⇓—regulation; ⇣—direct binding; ↑/↓—increase/decrease; Ʇ—inhibition.
Figure 2
Figure 2
Immunohistochemical localization of MUC1 and MUC5AC in the control colon (C), control liver (L) and hepatocellular carcinoma (HCC) samples. (A) MUC1 membranous localization in goblet cells of the normal colonic crypt; (B) MUC1-immunopositive biliary cells of interlobular ducts of the normal liver; (C) cytoplasmic expression of MUC1 in HCC neoplastic cells; (D) cytoplasmic localization of MUC5AC in numerous goblet cells of the control colonic crypts; (E) negative IHC reaction for MUC5AC in normal liver; (F) MUC5AC-immunopositive scattered neoplastic HCC cells. New polymer-based immunohistochemistry with 3,3′-Diaminobenzidine (DAB) as a chromogen. Haematoxylin counterstained. Objective × 40 (A–F) (our unpublished data).
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References

    1. Hanisch F.G. O-glycosylation of the mucin type. Biol. Chem. 2001;382:143–149. doi: 10.1515/BC.2001.022. - DOI - PubMed
    1. Corfield A. Eukaryotic protein glycosylation: A primer for histochemists and cell biologists. Histochem. Cell Biol. 2017;147:119–147. doi: 10.1007/s00418-016-1526-4. - DOI - PMC - PubMed
    1. Moniaux N., Escande F., Porchet N., Aubert J.P., Batra S.K. Structural organization and classification of the human mucin genes. Front. Biosci. 2001;6:D1192–D1206. doi: 10.2741/Moniaux. - DOI - PubMed
    1. Bergstrom K.S., Xia L. Mucin-type O-glycans and their roles in intestinal homeostasis. Glycobiology. 2013;23:1026–1037. doi: 10.1093/glycob/cwt045. - DOI - PMC - PubMed
    1. Corfield A.P. Mucins: A biologically relevant glycan barrier in mucosal protection. Biochim. Biophys. Acta. 2015;1850:236–252. doi: 10.1016/j.bbagen.2014.05.003. - DOI - PubMed