Open AccessHepatic Fibrosis and the Microenvironment: Fertile Soil for Hepatocellular Carcinoma Development
Author(s) -
M. Christopher Wallace,
Scott L. Friedman
Publication year - 2014
Publication title -
gene expression
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.591
H-Index - 46
eISSN - 1555-3884
pISSN - 1052-2166
DOI - 10.3727/105221614x13919976902057
Subject(s) - hepatocellular carcinoma , tumor microenvironment , cancer research , extracellular matrix , fibrosis , chronic liver disease , liver cancer , medicine , autophagy , cancer , liver disease , biology , pathology , cirrhosis , microbiology and biotechnology , apoptosis , biochemistry
Hepatocellular carcinoma is an emerging worldwide health threat that has few curative treatment options and poor overall survival. Progressive hepatic fibrosis is a common pathway for all forms of chronic liver disease and is closely linked epidemiologically to hepatocellular carcinoma risk. However, the molecular events that predispose a fibrotic liver to cancer development remain elusive. Nonetheless, a permissive hepatic microenvironment provides fertile soil for transition of damaged hepatocytes into hepatocellular carcinoma. Key predisposing features include alterations in the extracellular matrix, bidirectional signaling pathways between parenchymal and nonparenchymal cells, and immune dysfunction. Emerging research into the contributions of autophagy, tumor-associated fibroblasts, and hepatocellular carcinoma progenitor cells to this dangerous milieu also provides new mechanistic underpinnings to explain the contribution of fibrosis to cancer. As effective antifibrotic therapies are developed, these approaches could attenuate the rising surge of hepatocellular carcinoma associated with chronic liver disease.