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Cancer Cell. 2012 Apr 17;21(4):504-16. doi: 10.1016/j.ccr.2012.02.007.

Promotion of hepatocellular carcinoma by the intestinal microbiota and TLR4.

Author information

1
Department of Medicine, Columbia University, College of Physicians and Surgeons, New York, NY 10032, USA. rfs2102@columbia.edu

Abstract

Increased translocation of intestinal bacteria is a hallmark of chronic liver disease and contributes to hepatic inflammation and fibrosis. Here we tested the hypothesis that the intestinal microbiota and Toll-like receptors (TLRs) promote hepatocellular carcinoma (HCC), a long-term consequence of chronic liver injury, inflammation, and fibrosis. Hepatocarcinogenesis in chronically injured livers depended on the intestinal microbiota and TLR4 activation in non-bone-marrow-derived resident liver cells. TLR4 and the intestinal microbiota were not required for HCC initiation but for HCC promotion, mediating increased proliferation, expression of the hepatomitogen epiregulin, and prevention of apoptosis. Gut sterilization restricted to late stages of hepatocarcinogenesis reduced HCC, suggesting that the intestinal microbiota and TLR4 represent therapeutic targets for HCC prevention in advanced liver disease.

PMID:
22516259
PMCID:
PMC3332000
DOI:
10.1016/j.ccr.2012.02.007
[Indexed for MEDLINE]
Free PMC Article

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