Format

Send to

Choose Destination
Cancer Cell. 2009 Oct 6;16(4):295-308. doi: 10.1016/j.ccr.2009.08.021.

A lymphotoxin-driven pathway to hepatocellular carcinoma.

Author information

1
Department of Pathology, University Hospital Zurich, CH 8091 Zurich, Switzerland.

Erratum in

  • Cancer Cell. 2009 Nov 6;16(5):447.

Abstract

Hepatitis B and C viruses (HBV and HCV) cause chronic hepatitis and hepatocellular carcinoma (HCC) by poorly understood mechanisms. We show that cytokines lymphotoxin (LT) alpha and beta and their receptor (LTbetaR) are upregulated in HBV- or HCV-induced hepatitis and HCC. Liver-specific LTalphabeta expression in mice induces liver inflammation and HCC, causally linking hepatic LT overexpression to hepatitis and HCC. Development of HCC, composed in part of A6(+) oval cells, depends on lymphocytes and IKappa B kinase beta expressed by hepatocytes but is independent of TNFR1. In vivo LTbetaR stimulation implicates hepatocytes as the major LT-responsive liver cells, and LTbetaR inhibition in LTalphabeta-transgenic mice with hepatitis suppresses HCC formation. Thus, sustained LT signaling represents a pathway involved in hepatitis-induced HCC.

PMID:
19800575
PMCID:
PMC4422166
DOI:
10.1016/j.ccr.2009.08.021
[Indexed for MEDLINE]
Free PMC Article

Publication type, MeSH terms, Substances, Secondary source ID, Grant support

Publication type

MeSH terms

Substances

Secondary source ID

Grant support

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center