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
Pettersen Kristine, Amundsen Tore, Grønberg Bjørn H, Strasser Florian, Stephens Nathan, Hoem Dag, Molven Anders, Kaasa Stein, Fearon Kenneth, Jacobi Carsten, Sørhaug Sveinung, Skorpen Frank, Romundstad Pål R, Andersen Sonja, Degen Simone, Tadini Valentina, Grosjean Joël, Hatakeyama Shinji, Tesfahun Almaz N, Moestue Siver, Kim Jana, Nonstad Unni, Bjørkøy Geir
Units
PubMed
Doi
Citation
Type
Journal
Publication Date
Issn Electronic
Pages
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.