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Cytokines Are a Therapeutic Target for the Prevention of Inflammation-Induced Cancers

  • Conference paper
Cancer Prevention

Part of the book series: Recent Results in Cancer Research ((RECENTCANCER,volume 174))

Abstract

Interleukin-6 (IL-6) is an inflammatory cytokine with a well-documented role in cancer. The cytokine binds to a membrane-bound IL-6 receptor (IL-6R) and this complex associates with two molecules of the signal transducing protein gp130, initiating intracellular signaling. Whereas gp130 is expressed on all cells of the body, the IL-6R is only found on some cells, mainly hepatocytes and several leukocytes. Cells, which only express gp130 and no IL-6R, cannot respond to IL-6. We have shown that the IL-6R exists as a soluble protein generated by limited proteolysis of the membrane-bound receptor or by translation from an alternatively spliced mRNA. The complex of soluble IL-6R (sIL-6R) and IL-6 can bind to gp130 on cells that lack the membrane-bound IL-6R and trigger gp130 signaling. We have named this process trans-signaling. We review data that show that IL-6 uses classical signaling via the membrane-bound receptor and trans-signaling via the soluble receptor in physiological and pathophysiological situations. We have developed designer cytokines, which specifically enhance or inhibit IL-6 trans-signaling. These designer cytokines have been shown to be extremely useful in therapeutic applications such as blockade of chronic inflammation and cancer.

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  1. Biochemisches Institut, Christian-Albrechts-Universität zu Kiel, Olshausenstrasse 40, 24098, Kiel, Germany

    Stefan Rose-John (Prof. Dr.) & Heidi Schooltink (Dr. rer. nat.)

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  1. Stefan Rose-John
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  2. Heidi Schooltink
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  1. Tumor-Zentrum ZeTuP St. Gallen/Chur (Tumordiagnostik, Behandlung + Prävention), Rorschacherstr. 150, CH-9006, St. Gallen, Schweiz

    Hans-Jörg Senn  & Ursula Kapp  & 

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Rose-John, S., Schooltink, H. (2007). Cytokines Are a Therapeutic Target for the Prevention of Inflammation-Induced Cancers. In: Senn, HJ., Kapp, U. (eds) Cancer Prevention. Recent Results in Cancer Research, vol 174. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-37696-5_5

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  • DOI: https://doi.org/10.1007/978-3-540-37696-5_5

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