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J. Clin. Med. 2015, 4(12), 2028-2041; doi:10.3390/jcm4121958

Epithelial-to-Mesenchymal Transition and Cancer Invasiveness: What Can We Learn from Cholangiocarcinoma?

1
School of Medicine and Surgery, University of Milan-Bicocca, Via Cadore 48, 20900 Monza, Italy
2
Department of Molecular Medicine, University of Padua School of Medicine, Viale Colombo 3, 35131 Padua, Italy
3
Liver Center, Section of Digestive Diseases, Yale University, TAC Building, 333 Cedar Street, New Haven, CT 06520, USA
*
Author to whom correspondence should be addressed.
Academic Editors: David A. Brenner, Tatiana Kisseleva and Jonas Fuxe
Received: 19 November 2015 / Revised: 4 December 2015 / Accepted: 14 December 2015 / Published: 19 December 2015
(This article belongs to the Special Issue Epithelial-Mesenchymal Transition)
View Full-Text   |   Download PDF [493 KB, uploaded 19 December 2015]   |  

Abstract

In addition to its well-established role in embryo development, epithelial-to-mesenchymal transition (EMT) has been proposed as a general mechanism favoring tumor metastatization in several epithelial malignancies. Herein, we review the topic of EMT in cholangiocarcinoma (CCA), a primary liver cancer arising from the epithelial cells lining the bile ducts (cholangiocytes) and characterized by an abundant stromal reaction. CCA carries a dismal prognosis, owing to a pronounced invasiveness and scarce therapeutic opportunities. In CCA, several reports indicate that cancer cells acquire a number of EMT biomarkers and functions. These phenotypic changes are likely induced by both autocrine and paracrine signals released in the tumor microenvironment (cytokines, growth factors, morphogens) and intracellular stimuli (microRNAs, oncogenes, tumor suppressor genes) variably associated with specific disease mechanisms, including chronic inflammation and hypoxia. Nevertheless, evidence supporting a complete EMT of neoplastic cholangiocytes into stromal cells is lacking, and the gain of EMT-like changes by CCA cells rather reflects a shift towards an enhanced pro-invasive phenotype, likely induced by the tumor stroma. This concept may help to identify new biomarkers of early metastatic behavior along with potential therapeutic targets. View Full-Text
Keywords: cholangiocarcinoma; cholangiocyte; epithelial-to-mesenchymal transition; invasiveness; metastatization; tumor reactive stroma; cancer-associated fibroblast cholangiocarcinoma; cholangiocyte; epithelial-to-mesenchymal transition; invasiveness; metastatization; tumor reactive stroma; cancer-associated fibroblast
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Brivio, S.; Cadamuro, M.; Fabris, L.; Strazzabosco, M. Epithelial-to-Mesenchymal Transition and Cancer Invasiveness: What Can We Learn from Cholangiocarcinoma? J. Clin. Med. 2015, 4, 2028-2041.

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