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Sci Rep. 2017 May 17;7(1):2046. doi: 10.1038/s41598-017-02088-2.

Cancer cachexia associates with a systemic autophagy-inducing activity mimicked by cancer cell-derived IL-6 trans-signaling.

Author information

1
Department of Medical Laboratory Technology, Faculty of Natural Sciences, NTNU - Norwegian University of Science and Technology, 7491, Trondheim, Norway.
2
Centre of Molecular Inflammation Research and Department of Cancer Research and Molecular Medicine, NTNU - Norwegian University of Science and Technology, 7030, Trondheim, Norway.
3
Musculoskeletal Disease Area, Novartis Institutes for BioMedical Research Basel, Novartis Pharma AG, 4056, Basel, Switzerland.
4
Department of Laboratory Medicine, Children's and Women's Health, Faculty of Medicine and Health Sciences, NTNU - Norwegian University of Science and Technology, 7491, Trondheim, Norway.
5
Department of Circulation and Medical Imaging, Faculty of Medicine and Health Sciences, NTNU - Norwegian University of Science and Technology, 7491, Trondheim, Norway.
6
Department of Public Health and General Practice, Faculty of Medicine and Health Sciences, NTNU - Norwegian University of Science and Technology, 7491, Trondheim, Norway.
7
European Palliative Care Research Centre, Department of Cancer Research and Molecular Medicine, Faculty of Medicine and Health Sciences, NTNU - Norwegian University of Science and Technology, 7030, Trondheim, Norway.
8
Department of Thoracic Medicine, St.Olavs Hospital - Trondheim University Hospital, 7006, Trondheim, Norway.
9
The Cancer Clinic, St.Olavs Hospital - Trondheim University Hospital, 7030, Trondheim, Norway.
10
Department of Cancer Research and Molecular Medicine, Faculty of Medicine and Health Sciences, NTNU-Norwegian University of Science and Technology, Trondheim, Norway.
11
Oncological Palliative Medicine, Division ofClinic Oncology/Hematology, Department of Internal Medicine and Palliative Care Center, Cantonal Hospital, St. Gallen, Switzerland.
12
Clinical and Surgical Sciences, School of Clinical Sciences and Community Health, The University of Edinburgh, Royal Infirmary, N-5021, Edinburgh, UK.
13
Department of Gastrointestinal Surgery, Haukeland University Hospital, N-5020, Bergen, Norway.
14
Gade Laboratory for Pathology, Department of Clinical Medicine, University of Bergen, N-5021, Bergen, Norway.
15
Musculoskeletal Disease Area, Novartis Institutes for BioMedical Research Basel, Novartis Pharma AG, 4056, Basel, Switzerland. carsten.jacobi@novartis.com.
16
Department of Medical Laboratory Technology, Faculty of Natural Sciences, NTNU - Norwegian University of Science and Technology, 7491, Trondheim, Norway. geir.bjorkoy@ntnu.no.
17
Centre of Molecular Inflammation Research and Department of Cancer Research and Molecular Medicine, NTNU - Norwegian University of Science and Technology, 7030, Trondheim, Norway. geir.bjorkoy@ntnu.no.

Abstract

The majority of cancer patients with advanced disease experience weight loss, including loss of lean body mass. Severe weight loss is characteristic for cancer cachexia, a condition that significantly impairs functional status and survival. The underlying causes of cachexia are incompletely understood, and currently no therapeutic approach can completely reverse the condition. Autophagy coordinates lysosomal destruction of cytosolic constituents and is systemically induced by starvation. We hypothesized that starvation-mimicking signaling compounds secreted from tumor cells may cause a systemic acceleration of autophagy during cachexia. We found that IL-6 secreted by tumor cells accelerates autophagy in myotubes when complexed with soluble IL-6 receptor (trans-signaling). In lung cancer patients, were cachexia is prevalent, there was a significant correlation between elevated IL-6 expression in the tumor and poor prognosis of the patients. We found evidence for an autophagy-inducing bioactivity in serum from cancer patients and that this is clearly associated with weight loss. Importantly, the autophagy-inducing bioactivity was reduced by interference with IL-6 trans-signaling. Together, our findings suggest that IL-6 trans-signaling may be targeted in cancer cachexia.

PMID:
28515477
PMCID:
PMC5435723
DOI:
10.1038/s41598-017-02088-2
[Indexed for MEDLINE]
Free PMC Article

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