Expression and function of collagens in intrahepatic cholangiocarcinoma

Intrahepatic cholangiocarcinoma (iCCA) is an aggressive malignancy that originates from the biliary tract located within the liver parenchyma. While the incidence rate of iCCA is increasing worldwide, the existing therapeutic options still remain limited. Thus, the spread of iCCA is the foremost cause of treatment failure representing a major clinical challenge. The aggressive nature and refractoriness of the iCCA are strictly related to the desmoplastic tumor microenvironment, in which cancer cells are surrounded by inflammatory cells, cancer-associated fibroblasts, and the aberrant deposition of members of the collagen family. In recent years, accumulating evidence revealed that remodeling of collagens is pivotal in driving the dissemination of desmoplastic cancers. In this review, we describe the expression profile of collagens and their unique architecture in iCCA and how this can dictate neoplastic cell behavior. The emerging view argues for specific strategies aimed at targeting the collagen architecture that may be useful to hamper iCCA metastasis.