Publication

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

Journal Paper/Review - May 17, 2017

Units
PubMed
Doi

Citation
Pettersen K, Amundsen T, Grønberg B, Strasser F, Stephens N, Hoem D, Molven A, Kaasa S, Fearon K, Jacobi C, Sørhaug S, Skorpen F, Romundstad P, Andersen S, Degen S, Tadini V, Grosjean J, Hatakeyama S, Tesfahun A, Moestue S, Kim J, Nonstad U, Bjørkøy G. Cancer cachexia associates with a systemic autophagy-inducing activity mimicked by cancer cell-derived IL-6 trans-signaling. Sci Rep 2017; 7:2046.
Type
Journal Paper/Review (English)
Journal
Sci Rep 2017; 7
Publication Date
May 17, 2017
Issn Electronic
2045-2322
Pages
2046
Brief description/objective

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.