A lymphotoxin-driven pathway to hepatocellular carcinoma. - Archive ouverte HAL Access content directly
Journal Articles Cancer Cell Year : 2009

A lymphotoxin-driven pathway to hepatocellular carcinoma.

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Thomas Pietschmann

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.
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Dates and versions

inserm-00409700 , version 1 (06-10-2009)

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Johannes Haybaeck, Nicolas Zeller, Monika Julia Wolf, Achim Weber, Ulrich Wagner, et al.. A lymphotoxin-driven pathway to hepatocellular carcinoma.: Sustained hepatic LT signaling causes HCC. Cancer Cell, 2009, 16 (4), pp.295-308. ⟨10.1016/j.ccr.2009.08.021⟩. ⟨inserm-00409700⟩

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