Promotion of hepatocellular carcinoma by the intestinal microbiota and TLR4.
Cancer Cell
; 21(4): 504-16, 2012 Apr 17.
Article
em En
| MEDLINE
| ID: mdl-22516259
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Receptor 4 Toll-Like
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Intestinos
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Hepatopatias
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Neoplasias Hepáticas Experimentais
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article