Background
Intrahepatic cholangiocarcinoma (iCCA) is a malignancy that arises from the intrahepatic biliary tree, showing high mortality rates due to its late clinical presentation and limited treatment options. iCCA is characterized by a dense, reactive desmoplastic stroma marked by a dramatic accumulation of extracellular matrix (ECM). Although recent
Conclusions
Overall, this study contributes to the understanding of molecular basis underlying desmoplasia in iCCA and indicates the type III collagen as a promising therapeutic target.
Methods
iCCA ECM fibrillar structural organization was characterized by histological analysis. ECM proteome profiles from decellularized iCCA and surrounding noncancerous tissues were analysed by nLC coupled to MALDI-TOF/TOF analysis.
Results
iCCA tissues displayed high levels of collagen fibers and low abundance of reticular and elastic fibers, suggesting stiffness and loss of polarity. The ECM proteome profiles of iCCA samples, when compared to those obtained from the surrounding noncancerous tissues showed a dismantling of the basement membrane, a reduced angiogenesis and a downregulation of oncosuppressive activity. In particular, we focused on the effects of the overexpression of collagen type III alpha 1 chain (COL3A1) in iCCA, thus providing evidences that COL3A1 promotes iCCA cells migration and is a component of tumor-associated aligned collagen. Conclusions: Overall, this study contributes to the understanding of molecular basis underlying desmoplasia in iCCA and indicates the type III collagen as a promising therapeutic target.