Origin and role of hepatic myofibroblasts in hepatocellular carcinoma

Betul Gok Yavuz, Roberto Carmagnani Pestana, Yehia I. Abugabal, Sunil Krishnan, Jian Chen, Manal M. Hassan, Robert A. Wolff, Asif Rashid, Hesham M. Amin, Ahmed O. Kaseb

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

Hepatocellular carcinoma (HCC) is the most common primary liver cancer and is the second leading cause of cancer-related death worldwide. Fibrosis and cirrhosis are important risk factors for the development of HCC. Hepatic myofibroblasts are the cells responsible for extracellular matrix deposition, which is the hallmark of liver fibrosis. It is believed that myofibroblasts are predominantly derived from hepatic stellate cells (HSCs), also known as Ito cells. Nevertheless, depending on the nature of insult to the liver, it is thought that myofibroblasts may also originate from a variety of other cell types such as the portal fibroblasts (PFs), fibrocytes, hepatocytes, hepatic progenitor cells (HPCs), and mesothelial cells. Liver myofibroblasts are believed to transform into cancer-associated fibroblasts (CAFs) while HCC is developing. There is substantial evidence suggesting that activated HSCs (aHSCs)/cancer-associated fibroblasts (CAFs) may play an important role in HCC initiation and progression. In this paper, we aim to review current literature on cellular origins of myofibroblasts with a focus on hepatitis B virus (HBV)- and hepatitis C virus (HCV)-induced hepatic fibrosis. We also address the role of aHSCs/CAFs in HCC progression through the regulation of immune cells as well as mechanisms of evolvement of drug resistance.

Original languageEnglish (US)
Pages (from-to)1186-1201
Number of pages16
JournalOncotarget
Volume11
Issue number13
StatePublished - Mar 31 2020

Keywords

  • Hepatocellular carcinoma
  • Immunotherapy
  • Liver fibrosis
  • Myofibroblasts
  • Stellate cells

ASJC Scopus subject areas

  • Oncology

Fingerprint

Dive into the research topics of 'Origin and role of hepatic myofibroblasts in hepatocellular carcinoma'. Together they form a unique fingerprint.

Cite this