title: Periostin in intrahepatic cholangiocarcinoma: pathobiological insights and clinical implications.
abstract: Periostin is a modular glycoprotein frequently observed to be a major constituent of the extracellular milieu of mass-forming intrahepatic cholangiocarcinoma and other desmoplastic malignant tumors. In intrahepatic cholangiocarcinoma, as well as in desmoplastic pancreatic ductal adenocarcinoma, periostin is overexpressed and hypersecreted in large part, if not exclusively, by cancer-associated fibroblasts within the tumor stroma. Through its interaction with specific components of the extracellular tumor matrix, particularly collagen type I and tenascin-C, and with cell surface receptors, notably integrins leading to activation of the Akt and FAK signaling pathways, this TGF-β family-inducible matricellular protein appears to be functioning as a key extracellular matrix molecule regulating such critically important and diverse malignant tumor behaviors as tumor fibrogenesis and desmoplasia, invasive malignant cell growth, chemoresistance, and metastatic colonization. This review will discuss current evidence and basic molecular mechanisms implicating periostin as a mediator of intrahepatic cholangiocarcinoma invasive growth. In addition, its significance as a potential prognostic biomarker for intrahepatic cholangiocarcinoma patients, as well as future possibilities and challenges as a molecular target for cholangiocarcinoma therapy and/or prevention, will be critically evaluated.
authors.affiliation: Division of Cellular and Molecular Pathogenesis, Department of Pathology, Virginia Commonwealth University School of Medicine, Richmond, VA 23298-0297, United States. Electronic address: asirica@mcvh-vcu.edu.
authors.forename: Alphonse E
authors.initials: AE
authors.lastname: Sirica
authors.affiliation: Division of Cellular and Molecular Pathogenesis, Department of Pathology, Virginia Commonwealth University School of Medicine, Richmond, VA 23298-0297, United States.
authors.forename: Jorge A
authors.initials: JA
authors.lastname: Almenara
authors.affiliation: Division of Cellular and Molecular Pathogenesis, Department of Pathology, Virginia Commonwealth University School of Medicine, Richmond, VA 23298-0297, United States.
authors.forename: Chao
authors.initials: C
authors.lastname: Li
mesh_terms: D001650:Bile Duct Neoplasms / Q000378:metabolism* / Q000473:pathology*; D001653:Bile Ducts, Intrahepatic / Q000378:metabolism* / Q000473:pathology*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D018281:Cholangiocarcinoma / Q000378:metabolism* / Q000473:pathology*; D006801:Humans
chemical_list: D015815:Cell Adhesion Molecules; C512835:POSTN protein, human
keywords: Akt; Cancer-associated fibroblasts; Cholangiocarcinoma cell migration and invasion; Integrins; Metastasis; Periostin; Tumor desmoplasia