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
