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.

Overexpression of periostin and distinct mesothelin forms predict malignant progression in a rat cholangiocarcinoma model

“…While there have been many studies carried out on the functions of Msln and Postn, their role in cancer progression, including that of ICC, remains unclear and needs to be elucidated 8, 34, 40. Based on the data described herein, we propose that our unique rat cholangiocarcinoma models are ideal preclinical platforms for investigating Postn and Msln biology, regulation and functional relationships in the context of α‐SMA + CAF and cancer cell interactions promoting ICC progression, and the potential of Postn and Msln as molecular targets for ICC therapy.…”

“…In this context, the matricellular glycoprotein periostin (Postn) and the glycosylphosphatidylinositol‐anchored cell membrane glycoprotein mesothelin (Msln) have each been independently suggested as having potential as prognostic factors for human ICC 6, 7. Each may also provide opportunities for the development of novel targeted therapies for ICC 8, 9…”

“…Postn has been shown in both human and rat ICCs to be produced solely by α‐SMA + CAFs in the ICC stroma 6, 8. Its potential as an independent prognostic risk factor for poor survival for patients with ICC was first suggested by Utispan et al,6 who demonstrated that surgically resected ICC patients with tumors strongly immunostained for CAF‐Postn had significantly shorter postoperative survival times than those expressing low levels of Postn.…”

The role of microRNAs in intrahepatic cholangiocarcinoma

“…The dismal prognosis and aggressive progression associated with ICC have led researchers and clinicians to explore new avenues of potential treatment for ICC patients 58, 59, 60. Increasing evidence demonstrated that miRNAs are involved in important biological processes, including cell proliferation, differentiation, migration, invasion and apoptosis 61, 62, 63, 64, 65.…”

Our Panel of Experts Highlight the Most Important Research Articles Across the Spectrum of Topics Relevant to the Field of Hepatic Oncology

“…Thus, AHR and its ligands may be potentially valuable components to target in the treatment of cholangiocarcinoma. The integrin family has long been studied as having a potential role in the regulation of cholangiocarcinoma (CCC) [10][11][12]. Numerous studies have determined that specific integrins may activate the tumor progression and invasion of CCC [10,11].…”