Quick Search:

uzh logo
Browse by:
bullet
bullet
bullet
bullet

Zurich Open Repository and Archive

Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-23643

Haybaeck, J; Zeller, N; Wolf, M J; Weber, A; Wagner, U; Kurrer, M O; Bremer, J; Iezzi, G; Graf, R; Clavien, P A; Thimme, R; Blum, H; Nedospasov, S A; Zatloukal, K; Ramzan, M; Ciesek, S; Pietschmann, T; Marche, P N; Karin, M; Kopf, M; Browning, J L; Aguzzi, A; Heikenwalder, M (2009). A lymphotoxin-driven pathway to hepatocellular carcinoma. Cancer Cell, 16(4):295-308.

[img] PDF - Registered users only
4MB

View at publisher

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.

Citations

127 citations in Web of Science®
123 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

0 downloads since deposited on 03 Nov 2009
0 downloads since 12 months

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Functional Genomics Center Zurich
04 Faculty of Medicine > University Hospital Zurich > Institute of Neuropathology
04 Faculty of Medicine > University Hospital Zurich > Institute of Surgical Pathology
04 Faculty of Medicine > University Hospital Zurich > Clinic for Visceral and Transplantation Surgery
04 Faculty of Medicine > University Hospital Zurich > Division of Surgical Research
08 University Research Priority Programs > Systems Biology / Functional Genomics
DDC:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2009
Deposited On:03 Nov 2009 16:15
Last Modified:27 Nov 2013 20:36
Publisher:Elsevier
ISSN:1535-6108
Publisher DOI:10.1016/j.ccr.2009.08.021
PubMed ID:19800575

Users (please log in): suggest update or correction for this item

Repository Staff Only: item control page