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Semin Liver Dis 2020; 40(03): 307-320
DOI: 10.1055/s-0040-1708876
Review Article

Hepatic Stellate Cell–Macrophage Crosstalk in Liver Fibrosis and Carcinogenesis

Michitaka Matsuda
1   Division of Digestive and Liver Diseases, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California
,
Ekihiro Seki
1   Division of Digestive and Liver Diseases, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California
2   Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California
› Author Affiliations Funding This work was supported by the National Institutes of Health grants R01AA027036, R01DK085252, R21AA025841, and P01CA233452 and by Cedars-Sinai Medical Center (Cedars-Sinai Cancer Center for Integrated Research in Cancer and Lifestyle Award).
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Abstract

Chronic liver injury due to viral hepatitis, alcohol abuse, and metabolic disorders is a worldwide health concern. Insufficient treatment of chronic liver injury leads to fibrosis, causing liver dysfunction and carcinogenesis. Most cases of hepatocellular carcinoma (HCC) develop in the fibrotic liver. Pathological features of liver fibrosis include extracellular matrix (ECM) accumulation, mesenchymal cell activation, immune deregulation, and angiogenesis, all of which contribute to the precancerous environment, supporting tumor development. Among liver cells, hepatic stellate cells (HSCs) and macrophages play critical roles in fibrosis and HCC. These two cell types interplay and remodel the ECM and immune microenvironment in the fibrotic liver. Once HCC develops, HCC-derived factors influence HSCs and macrophages to switch to protumorigenic cell populations, cancer-associated fibroblasts and tumor-associated macrophages, respectively. This review aims to summarize currently available data on the roles of HSCs and macrophages in liver fibrosis and HCC, with a focus on their interaction.

Keywords

cancer-associated fibroblasts - tumor-associated macrophages - extracellular matrix - hepatocellular carcinoma - cirrhosis


Publication History

Article published online:
02 April 2020

© 2020. Thieme. All rights reserved.

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