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Semin Liver Dis 2020; 40(03): 282-297
DOI: 10.1055/s-0040-1705109
Review Article

Liver Matrix in Benign and Malignant Biliary Tract Disease

Luca Fabris
1   Department of Molecular Medicine, University of Padua, Padua, Italy
2   Liver Center, Department of Medicine, Yale University, New Haven, Connecticut
,
Massimiliano Cadamuro
1   Department of Molecular Medicine, University of Padua, Padua, Italy
,
Silvia Cagnin
1   Department of Molecular Medicine, University of Padua, Padua, Italy
,
Mario Strazzabosco
2   Liver Center, Department of Medicine, Yale University, New Haven, Connecticut
,
Gregory J. Gores
3   Division of Gastroenterology and Hepatology and the Mayo Clinic Center for Cell Signaling in Gastroenterology, Mayo Clinic, Rochester, Michigan
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Abstract

The extracellular matrix is a highly reactive scaffold formed by a wide array of multifunctional molecules, encompassing collagens and noncollagenous glycoproteins, proteoglycans, glycosaminoglycans, and polysaccharides. Besides outlining the tissue borders, the extracellular matrix profoundly regulates the behavior of resident cells by transducing mechanical signals, and by integrating multiple cues derived from the microenvironment. Evidence is mounting that changes in the biostructure of the extracellular matrix are instrumental for biliary repair. Following biliary damage and eventually, malignant transformation, the extracellular matrix undergoes several quantitative and qualitative modifications, which direct interactions among hepatic progenitor cells, reactive ductular cells, activated myofibroblasts and macrophages, to generate the ductular reaction. Herein, we will give an overview of the main molecular factors contributing to extracellular matrix remodeling in cholangiopathies. Then, we will discuss the structural alterations in terms of biochemical composition and physical stiffness featuring the “desmoplastic matrix” of cholangiocarcinoma along with their pro-oncogenic effects.

Keywords

basement membrane - cholangiocytes - ductular reaction - tumor reactive stroma - biliary fibrosis

Financial Support

L.F. was supported by Progetti di Ricerca di Dipartimento (PRID-DMM) 2017, University of Padua; M.S. was supported by the National Institutes of Health RO1DK096096I, by DK034989 Silvio O. Conte Digestive Diseases Research Core Center, and by PSC Partners Seeking a Cure; G.J.G. was supported by Chris M. Carlos and Catharine Nicole Jockisch Carlos Endowment Fund in Primary Sclerosing Cholangitis.




Publication History

Article published online:
11 March 2020

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