Origin and role of hepatic myofibroblasts in hepatocellular carcinoma
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Betul Gok Yavuz1,2, Roberto Carmagnani Pestana2, Yehia I. Abugabal2, Sunil Krishnan3, Jian Chen4, Manal M. Hassan5, Robert A. Wolff2, Asif Rashid6, Hesham M. Amin7,8 and Ahmed O. Kaseb2
1 Department of Basic Oncology, Hacettepe University Cancer Institute, Ankara, Turkey
2 Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
3 Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
4 Department of Gastroenterology, Hepatology, and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
5 Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
6 Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
7 Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
8 MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, Houston, TX, USA
|Ahmed O. Kaseb,||email:||[email protected]|
|Hesham M. Amin,||email:||[email protected]|
Keywords: hepatocellular carcinoma; stellate cells; myofibroblasts; liver fibrosis; immunotherapy
Received: September 02, 2019 Accepted: March 03, 2020 Published: March 31, 2020
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.
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