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IL-6 trans-signaling is essential for the development of hepatocellular carcinoma in mice

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IL-6 trans-signaling is essential for the development of hepatocellular carcinoma in mice. / Bergmann, Juri; Müller, Miryam; Baumann, Niklas; Reichert, Manuel; Heneweer, Carola; Bolik, Julia; Lücke, Karsten; Gruber, Sabine; Carambia, Antonella; Boretius, Susanne; Leuschner, Ivo; Becker, Thomas; Rabe, Björn; Herkel, Johannes; Wunderlich, F Thomas; Mittrücker, Hans-Willi; Rose-John, Stefan; Schmidt-Arras, Dirk.

in: HEPATOLOGY, Jahrgang 65, Nr. 1, 01.2017, S. 89-103.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Bergmann, J, Müller, M, Baumann, N, Reichert, M, Heneweer, C, Bolik, J, Lücke, K, Gruber, S, Carambia, A, Boretius, S, Leuschner, I, Becker, T, Rabe, B, Herkel, J, Wunderlich, FT, Mittrücker, H-W, Rose-John, S & Schmidt-Arras, D 2017, 'IL-6 trans-signaling is essential for the development of hepatocellular carcinoma in mice', HEPATOLOGY, Jg. 65, Nr. 1, S. 89-103. https://doi.org/10.1002/hep.28874

APA

Bergmann, J., Müller, M., Baumann, N., Reichert, M., Heneweer, C., Bolik, J., Lücke, K., Gruber, S., Carambia, A., Boretius, S., Leuschner, I., Becker, T., Rabe, B., Herkel, J., Wunderlich, F. T., Mittrücker, H-W., Rose-John, S., & Schmidt-Arras, D. (2017). IL-6 trans-signaling is essential for the development of hepatocellular carcinoma in mice. HEPATOLOGY, 65(1), 89-103. https://doi.org/10.1002/hep.28874

Vancouver

Bergmann J, Müller M, Baumann N, Reichert M, Heneweer C, Bolik J et al. IL-6 trans-signaling is essential for the development of hepatocellular carcinoma in mice. HEPATOLOGY. 2017 Jan;65(1):89-103. https://doi.org/10.1002/hep.28874

Bibtex

@article{b89992b82ce843ddb8ba9aa5dc04d9af,
title = "IL-6 trans-signaling is essential for the development of hepatocellular carcinoma in mice",
abstract = "Hepatocellular carcinoma (HCC) is one of the most frequent tumors worldwide with rising incidence. The inflammatory cytokine, interleukin-6 (IL-6), is a critical mediator of HCC development. It can signal through two distinct pathways: the IL-6 classic and the IL-6 trans-signaling pathway. Whereas IL-6 classic signaling is important for innate and acquired immunity, IL-6 trans-signaling has been linked to accelerated liver regeneration and several chronic inflammatory pathologies. However, its implication in liver tumorigenesis has not been addressed yet. Here, we show that IL-6 trans-signaling, but not IL-6 classic signaling, is essential to promote hepatocellular carcinogenesis by two mechanisms: First, it prevents DNA-damage-induced hepatocyte apoptosis through suppression of p53 and enhances β-catenin activation and tumor proliferation. Second, IL-6 trans-signaling directly induces endothelial cell proliferation to promote tumor angiogenesis. Consequently, soluble gp130 fused to Fc transgenic mice lacking IL-6 trans-signaling are largely protected from tumor formation in a diethylnitrosamine/3,3',5,5'-tetrachloro-1,4-bis(pyridyloxy)benzene model of HCC.CONCLUSION: IL-6 trans-signaling, and not IL-6 classic signaling, is mandatory for development of hepatocellular carcinogenesis. Therefore, specific inhibition of IL-6 trans-signaling, rather than total inhibition of IL-6 signaling, is sufficient to blunt tumor initiation and impair tumor progression without compromising IL-6 classic signaling-driven protective immune responses. (Hepatology 2017;65:89-103).",
keywords = "Animals, Carcinoma, Hepatocellular, Interleukin-6, Liver Neoplasms, Male, Mice, Signal Transduction, Journal Article, Research Support, Non-U.S. Gov't",
author = "Juri Bergmann and Miryam M{\"u}ller and Niklas Baumann and Manuel Reichert and Carola Heneweer and Julia Bolik and Karsten L{\"u}cke and Sabine Gruber and Antonella Carambia and Susanne Boretius and Ivo Leuschner and Thomas Becker and Bj{\"o}rn Rabe and Johannes Herkel and Wunderlich, {F Thomas} and Hans-Willi Mittr{\"u}cker and Stefan Rose-John and Dirk Schmidt-Arras",
note = "{\textcopyright} 2016 by the American Association for the Study of Liver Diseases.",
year = "2017",
month = jan,
doi = "10.1002/hep.28874",
language = "English",
volume = "65",
pages = "89--103",
journal = "HEPATOLOGY",
issn = "0270-9139",
publisher = "John Wiley and Sons Ltd",
number = "1",

}

RIS

TY - JOUR

T1 - IL-6 trans-signaling is essential for the development of hepatocellular carcinoma in mice

AU - Bergmann, Juri

AU - Müller, Miryam

AU - Baumann, Niklas

AU - Reichert, Manuel

AU - Heneweer, Carola

AU - Bolik, Julia

AU - Lücke, Karsten

AU - Gruber, Sabine

AU - Carambia, Antonella

AU - Boretius, Susanne

AU - Leuschner, Ivo

AU - Becker, Thomas

AU - Rabe, Björn

AU - Herkel, Johannes

AU - Wunderlich, F Thomas

AU - Mittrücker, Hans-Willi

AU - Rose-John, Stefan

AU - Schmidt-Arras, Dirk

N1 - © 2016 by the American Association for the Study of Liver Diseases.

PY - 2017/1

Y1 - 2017/1

N2 - Hepatocellular carcinoma (HCC) is one of the most frequent tumors worldwide with rising incidence. The inflammatory cytokine, interleukin-6 (IL-6), is a critical mediator of HCC development. It can signal through two distinct pathways: the IL-6 classic and the IL-6 trans-signaling pathway. Whereas IL-6 classic signaling is important for innate and acquired immunity, IL-6 trans-signaling has been linked to accelerated liver regeneration and several chronic inflammatory pathologies. However, its implication in liver tumorigenesis has not been addressed yet. Here, we show that IL-6 trans-signaling, but not IL-6 classic signaling, is essential to promote hepatocellular carcinogenesis by two mechanisms: First, it prevents DNA-damage-induced hepatocyte apoptosis through suppression of p53 and enhances β-catenin activation and tumor proliferation. Second, IL-6 trans-signaling directly induces endothelial cell proliferation to promote tumor angiogenesis. Consequently, soluble gp130 fused to Fc transgenic mice lacking IL-6 trans-signaling are largely protected from tumor formation in a diethylnitrosamine/3,3',5,5'-tetrachloro-1,4-bis(pyridyloxy)benzene model of HCC.CONCLUSION: IL-6 trans-signaling, and not IL-6 classic signaling, is mandatory for development of hepatocellular carcinogenesis. Therefore, specific inhibition of IL-6 trans-signaling, rather than total inhibition of IL-6 signaling, is sufficient to blunt tumor initiation and impair tumor progression without compromising IL-6 classic signaling-driven protective immune responses. (Hepatology 2017;65:89-103).

AB - Hepatocellular carcinoma (HCC) is one of the most frequent tumors worldwide with rising incidence. The inflammatory cytokine, interleukin-6 (IL-6), is a critical mediator of HCC development. It can signal through two distinct pathways: the IL-6 classic and the IL-6 trans-signaling pathway. Whereas IL-6 classic signaling is important for innate and acquired immunity, IL-6 trans-signaling has been linked to accelerated liver regeneration and several chronic inflammatory pathologies. However, its implication in liver tumorigenesis has not been addressed yet. Here, we show that IL-6 trans-signaling, but not IL-6 classic signaling, is essential to promote hepatocellular carcinogenesis by two mechanisms: First, it prevents DNA-damage-induced hepatocyte apoptosis through suppression of p53 and enhances β-catenin activation and tumor proliferation. Second, IL-6 trans-signaling directly induces endothelial cell proliferation to promote tumor angiogenesis. Consequently, soluble gp130 fused to Fc transgenic mice lacking IL-6 trans-signaling are largely protected from tumor formation in a diethylnitrosamine/3,3',5,5'-tetrachloro-1,4-bis(pyridyloxy)benzene model of HCC.CONCLUSION: IL-6 trans-signaling, and not IL-6 classic signaling, is mandatory for development of hepatocellular carcinogenesis. Therefore, specific inhibition of IL-6 trans-signaling, rather than total inhibition of IL-6 signaling, is sufficient to blunt tumor initiation and impair tumor progression without compromising IL-6 classic signaling-driven protective immune responses. (Hepatology 2017;65:89-103).

KW - Animals

KW - Carcinoma, Hepatocellular

KW - Interleukin-6

KW - Liver Neoplasms

KW - Male

KW - Mice

KW - Signal Transduction

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1002/hep.28874

DO - 10.1002/hep.28874

M3 - SCORING: Journal article

C2 - 27770462

VL - 65

SP - 89

EP - 103

JO - HEPATOLOGY

JF - HEPATOLOGY

SN - 0270-9139

IS - 1

ER -