The Role of Fibrosis and Liver-Associated Fibroblasts in the Pathogenesis of Hepatocellular Carcinoma

International Journal of Molecular Sciences

DavidA. Brenner¹  Jacopo Baglieri¹  Tatiana Kisseleva² 

[1] Department of Medicine, UC San Diego, La Jolla, CA 92093, USA;Department of Surgery, UC San Diego, La Jolla, CA 92093, USA;

关键词: hepatocellular carcinoma (HCC);    fibrosis;    cancer-associated fibroblasts (CAFs);    hepatic stellate cells (HSCs);    tumor microenvironment;   

DOI  :  10.3390/ijms20071723

来源: DOAJ

【 摘 要 】

Hepatocellular carcinoma (HCC) is one of the most aggressive types of cancer and lacks effective therapeutic approaches. Most HCC develops in the setting of chronic liver injury, hepatic inflammation, and fibrosis. Hepatic stellate cells (HSCs) and cancer-associated fibroblasts (CAFs) are key players in liver fibrogenesis and hepatocarcinogenesis, respectively. CAFs, which probably derive from HSCs, activate into extracellular matrix (ECM)-producing myofibroblasts and crosstalk with cancer cells to affect tumor growth and invasion. In this review, we describe the different components which form the HCC premalignant microenvironment (PME) and the tumor microenvironment (TME), focusing on the liver fibrosis process and the biology of CAFs. We will describe the CAF-dependent mechanisms which have been suggested to promote hepatocarcinogenesis, such as the alteration of ECM, CAF-dependent production of cytokines and angiogenic factors, CAF-dependent reduction of immuno-surveillance, and CAF-dependent promotion of epithelial-mesenchymal transition (EMT). New knowledge of the fibrosis process and the role of CAFs in HCC may pave the way for new therapeutic strategies for liver cancer.

【 授权许可】

Unknown