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The Role of Interleukin-6/GP130 Cytokines in Cancer Cachexia

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The Systemic Effects of Advanced Cancer

Abstract

Cancer cachexia is characterized by the involuntary loss of skeletal muscle with or without adipose tissue loss in the presence of tumor burden. It is a prevalent yet clinically unmet need that results in devastating systemic wasting effects. Chronic inflammation triggers cancer progression and is observed in cachexia. This review will highlight the Interleukin-6 (IL-6) family of cytokines, including IL-6 itself, Leukemia Inhibitory Factor (LIF), Ciliary Neurotrophic Factor (CNTF), Cardiotrophin-1 (CT-1), Oncostatin M (OSM), Interleukin-11 (IL-11), Interleukin-27 (IL-27), and Cardiotrophin-like cytokine (CLC), which all share signaling through IL-6 Signal Transducer (IL6ST), also known as Glycoprotein 130 (GP130) to activate common downstream pathways including the JAK/STAT, MAPK, and AKT pathways. IL-6 has been long linked to cancer cachexia through both associative and functional studies; furthermore, anti-IL-6 therapies have been trialed in patients. Recently, LIF has emerged as a novel cachexia mediator in experimental systems. Far less is known about the other cytokines in cachexia, although they have suggestive properties on adipose and muscle tissues in other contexts. Future studies are required to determine the roles of these other factors in cancer cachexia and their potential for designing therapies.

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Acknowledgements

We would like to acknowledge Kellie N. Kaneshiro from the IU School of Medicine Ruth Lilly Medical Library for her contributions in the literature review search and library preparation. Art is adapted from Servier Medical Art (servier.com) used under a Creative Commons Attribution 3.0 Unported License. T.A.Z. is supported in part by the National Institute for Arthritis and Musculoskeletal and Skin Diseases (NIAMS grant R21AR074908), the National Cancer Institute (grant R01CA194593), and the Veterans Administration (grants I01BX004177 and I01CX002046). D.H.A.J. is funded in part by the Adam W. Herbert Ph.D. Fellowship from Indiana University and the Cancer Biology Training Program Fellowship from the IU Simon Cancer Center.

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, Indianapolis, IN, USA

    Daenique H. A. Jengelley & Teresa A. Zimmers

  2. Department of Surgery, Indianapolis, IN, USA

    Teresa A. Zimmers

  3. Department of Anatomy, Cell Biology, & Physiology, Indianapolis, IN, USA

    Teresa A. Zimmers

  4. Department of Otolaryngology—Head & Neck Surgery, Indiana University School of Medicine, Indianapolis, IN, USA

    Teresa A. Zimmers

  5. Research Service, Richard L. Roudebush Veterans Administration Medical Center, Indianapolis, IN, USA

    Teresa A. Zimmers

  6. Indiana Center for Musculoskeletal Health, Indianapolis, IN, USA

    Teresa A. Zimmers

  7. Indiana University Simon Comprehensive Cancer Center, Indianapolis, IN, USA

    Teresa A. Zimmers

Authors
  1. Daenique H. A. Jengelley
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  2. Teresa A. Zimmers
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Correspondence to Teresa A. Zimmers .

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Editors and Affiliations

  1. Columbia University Irving Medical Center, New York, NY, USA

    Swarnali Acharyya

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Jengelley, D.H.A., Zimmers, T.A. (2022). The Role of Interleukin-6/GP130 Cytokines in Cancer Cachexia. In: Acharyya, S. (eds) The Systemic Effects of Advanced Cancer. Springer, Cham. https://doi.org/10.1007/978-3-031-09518-4_6

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