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Semin Liver Dis 2019; 39(03): 315-333
DOI: 10.1055/s-0039-1685539
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Contributions of Fibroblasts, Extracellular Matrix, Stiffness, and Mechanosensing to Hepatocarcinogenesis

Aveline Filliol
1   Department of Medicine, Columbia University, College of Physicians and Surgeons, New York
,
Robert F. Schwabe
1   Department of Medicine, Columbia University, College of Physicians and Surgeons, New York
2   Institute of Human Nutrition, Columbia University, College of Physicians and Surgeons, New York, New York
› Author Affiliations
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Publication History

Publication Date:
21 June 2019 (online)

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Abstract

Hepatocellular carcinoma (HCC) is the third leading cause of cancer mortality worldwide. A unique feature of liver cancer is its close association with liver fibrosis. About 90% of HCCs develop in advanced liver fibrosis or cirrhosis, suggesting an important role for the fibrotic microenvironment in driving HCC development. Here, the authors will discuss functional contributions of liver fibrosis to the development of HCC, focusing on mechanisms through which fibrosis may promote HCC development such as hepatic stellate cell-derived extracellular matrix, growth factors, and cytokines, stiffness-induced signaling pathways, and immunosuppression. Better understanding of these factors in HCC development and progression may provide the basis for novel stromal-based therapies for tumor prevention or therapy.

Keywords

Cancer-associated fibroblast - fibroblast heterogeneity - mechanosensitive signaling - YAP - TAZ - integrin