Fibrosis-dependent mechanisms of hepatocarcinogenesis
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Open Access
- 1 March 2012
- journal article
- review article
- Published by Ovid Technologies (Wolters Kluwer Health) in Hepatology
- Vol. 56 (2), 769-775
- https://doi.org/10.1002/hep.25670
Abstract
Hepatocellular carcinoma (HCC) is a rising worldwide cause of cancer mortality, making the elucidation of its underlying mechanisms an urgent priority. The liver is unique in its response to injury, simultaneously undergoing regeneration and fibrosis. HCC occurs in the context of these two divergent responses, leading to distinctive pathways of carcinogenesis. In this review we highlight pathways of liver tumorigenesis that depend on, or are enhanced by, fibrosis. Activated hepatic stellate cells drive fibrogenesis, changing the composition of the extracellular matrix. Matrix quantity and stiffness also increase, providing a reservoir for bound growth factors. In addition to promoting angiogenesis, these factors may enhance the survival of both preneoplastic hepatocytes and activated hepatic stellate cells. Fibrotic changes also modulate the activity of inflammatory cells in the liver, reducing the activity of natural killer and natural killer T cells that normally contribute to tumor surveillance. These pathways synergize with inflammatory signals, including telomerase reactivation and reactive oxygen species release, ultimately resulting in cancer. Clarifying fibrosis‐dependent tumorigenic mechanisms will help rationalize antifibrotic therapies as a strategy to prevent and treat HCC. (HEPATOLOGY 2012)Keywords
This publication has 82 references indexed in Scilit:
- LTBPs, more than just an escort serviceJournal of Cellular Biochemistry, 2012
- Matrix stiffness modulates proliferation, chemotherapeutic response, and dormancy in hepatocellular carcinoma cellsHepatology, 2010
- Accumulation of natural killer T cells in progressive nonalcoholic fatty liver diseaseHepatology, 2010
- Hedgehog signaling is critical for normal liver regeneration after partial hepatectomy in miceHepatology, 2010
- Matrix Crosslinking Forces Tumor Progression by Enhancing Integrin SignalingCell, 2009
- The role of stem cells in liver repair and fibrosisThe International Journal of Biochemistry & Cell Biology, 2009
- Diverse roles of invariant natural killer T cells in liver injury and fibrosis induced by carbon tetrachlorideHepatology, 2008
- Free radicals and antioxidants in normal physiological functions and human diseaseThe International Journal of Biochemistry & Cell Biology, 2007
- Cellular and molecular mechanisms of fibrosisThe Journal of Pathology, 2007
- Assessment of Hepatic Fibrosis With Magnetic Resonance ElastographyClinical Gastroenterology and Hepatology, 2007