Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Haybaeck, J; Zeller, N; Wolf, MJ; Weber, A; Wagner, U; Kurrer, MO; Bremer, J; Iezzi, G; Graf, R; Clavien, PA; Thimme, R; Blum, H; Nedospasov, SA; Zatloukal, K; Ramzan, M; Ciesek, S; Pietschmann, T; Marche, PN; Karin, M; Kopf, M; Browning, JL; Aguzzi, A; Heikenwalder, M.
A lymphotoxin-driven pathway to hepatocellular carcinoma.
CANCER CELL. 2009; 16(4): 295-308.
Doi: 10.1016/j.ccr.2009.08.021
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- Führende Autor*innen der Med Uni Graz
- Haybäck Johannes
- Co-Autor*innen der Med Uni Graz
- Zatloukal Kurt
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- 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Carcinoma, Hepatocellular - genetics Carcinoma, Hepatocellular - immunology Carcinoma, Hepatocellular - virology
- Case-Control Studies -
- Cell Transformation, Viral -
- Chemokines - metabolism
- Chromosome Aberrations -
- Gene Expression Regulation, Neoplastic -
- Hepatitis B, Chronic - immunology
- Hepatitis C, Chronic - immunology
- Hepatocytes - immunology Hepatocytes - virology
- Homeodomain Proteins - genetics Homeodomain Proteins - metabolism
- Humans -
- I-kappa B Kinase - genetics I-kappa B Kinase - metabolism
- Ligands -
- Liver - immunology Liver - virology
- Liver Neoplasms - genetics Liver Neoplasms - immunology Liver Neoplasms - virology
- Lymphocytes - immunology Lymphocytes - virology
- Lymphotoxin beta Receptor - genetics Lymphotoxin beta Receptor - metabolism
- Lymphotoxin-alpha - genetics Lymphotoxin-alpha - metabolism
- Lymphotoxin-beta - genetics Lymphotoxin-beta - metabolism
- Male -
- Mice -
- Mice, Inbred C57BL -
- Mice, Knockout -
- Mice, Transgenic -
- RNA, Messenger - metabolism
- Receptors, Tumor Necrosis Factor, Type I - genetics Receptors, Tumor Necrosis Factor, Type I - metabolism
- Receptors, Tumor Necrosis Factor, Type II - genetics Receptors, Tumor Necrosis Factor, Type II - metabolism
- Recombinant Proteins - metabolism
- Signal Transduction -
- Tumor Markers, Biological - metabolism
- Tumor Necrosis Factor Ligand Superfamily Member 14 - metabolism
- Tumor Necrosis Factor-alpha - metabolism
- Up-Regulation -