C2 - Molecular mechanisms in progression of inflammation-induced HCC: contribution of heme oxygenase 1

C2_April 2014

Principal Investigators:
Dr. rer. nat. Roja Barikbin
Institute of Experimental Immunology & Hepatology
University Medical Center Hamburg-Eppendorf
Martinistr. 52
20246 Hamburg
Tel.: +49-40-7410-51886
E-Mail: r.barikbin@uke.de

Prof. Dr. rer. nat. Gisa Tiegs
Institute of Experimental Immunology & Hepatology
University Medical Center Hamburg-Eppendorf
Martinistr. 52
20246 Hamburg
Tel.: +49-40-7410-58731
Fax: +49-40-7410-57150
E-Mail: g.tiegs@uke.de

Project description

Chronic liver inflammation is a dynamic progress, leading to fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Processes of liver regeneration and immune regulation are involved in carcinogenesis, however underlying mechanisms still need to be investigated.

HCC therapy is limited. Elucidating the molecular mechanisms of liver regeneration, immune-regulation and tumorigenic processes is essential for development of new therapies.

C2 in 60 SecondsVideoarchiv

online seit 25.06.2014
C2_Working hypothesis
Figure 1: Our Hypothesis: Chronic liver inflammation induces a permanent endogenous immune regulation that might support tumor development. Early interference with inflammation, by induction of HO-1, suppresses immune regulation and reduces the cancer risk.

We could show, that induction of the anti-inflammatory enzyme heme oxygenase 1 (HO-1), in a mouse model of chronic liver inflammation and tumor progression, protects from inflammation and fibrosis formation. Furthermore HO-1 induction delays tumor-promoting regeneration and proliferation processes.

Now we want to investigate the endogenous immune regulation in chronic inflammation and tumor development, and the influence of HO-1 induction on immune-regulation. In a therapeutic approach we want to interfere tumor growth by depletion of tumor-promoting immune populations.

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Stoyanov E, Ludwig G, Mizrahi L, Olam D, Schnitzer-Perlman T, Tasika E, Sass G, Tiegs G, Jiang Y, Nie T, Kohler J, Schinazi RF, Vertino PM, Cedar H, Galun E, Goldenberg D

Chronic liver inflammation modifies DNA methylation at the precancerous stage of murine hepatocarcinogenesis
Oncotarget. 2015 May 10;6(13):11047-60.

Wuestenberg A, Kah J, Singethan K, Sirma H, Keller AD, Rosal SR, Schrader J, Loscher C, Volz T, Bartenschlager R, Lohmann V, Protzer U, Dandri M, Lohse AW, Tiegs G, Sass G. (2014)
Matrix Conditions and KLF2-Dependent Induction of Heme Oxygenase-1 Modulate Inhibition of HCV Replication by Fluvastatin.
PLoS ONE 9(5): e96533. doi:10.1371/journal.pone.0096533

Barikbin R, Neureiter D, Wirth J, Erhardt A, Schwinge D, Kluwe J, Schramm C, Tiegs G, Sass G. (2012)
Induction of heme oxygenase 1 prevents progression of liver fibrosis in Mdr2 knockout mice
Hepatology. 2012 Feb;55(2):553-62. doi: 10.1002/hep.24711

Sass G, Barikbin R, Tiegs G. (2012)
The multiple functions of heme oxygenase-1 in the liver
Z Gastroenterol. 2012 Jan;50(1):34-40. doi: 10.1055/s-0031-1282046. Epub 2012 Jan 5.