Cancer cachexia associates with a systemic autophagy-inducing activity mimicked by cancer cell-derived IL-6 trans-signaling
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 understo...
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creator | Pettersen, Kristine Andersen, Sonja Benedikte Degen, simone Tadini, Valentina Grosjean, Joel Hatakeyama, Shinji Tesfahun, Almaz Nigatu Moestue, Siver Andreas Kim, Jana Nonstad, Unni Romundstad, Pål Richard Skorpen, Frank Sørhaug, Sveinung Amundsen, Tore Grønberg, Bjørn Henning Strasser, Florian Stephens, Nathan Hoem, Dag Molven, Anders Kaasa, Stein Fearon, Kenneth Jacobi, Carsten Bjørkøy, Geir |
description | 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 autophagyinducing 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. |
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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 autophagyinducing 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.</description><language>eng</language><publisher>Nature Publishing Group</publisher><creationdate>2017</creationdate><rights>info:eu-repo/semantics/openAccess</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,780,885,26566</link.rule.ids><linktorsrc>$$Uhttp://hdl.handle.net/11250/2480265$$EView_record_in_NORA$$FView_record_in_$$GNORA$$Hfree_for_read</linktorsrc></links><search><creatorcontrib>Pettersen, Kristine</creatorcontrib><creatorcontrib>Andersen, Sonja Benedikte</creatorcontrib><creatorcontrib>Degen, simone</creatorcontrib><creatorcontrib>Tadini, Valentina</creatorcontrib><creatorcontrib>Grosjean, Joel</creatorcontrib><creatorcontrib>Hatakeyama, Shinji</creatorcontrib><creatorcontrib>Tesfahun, Almaz Nigatu</creatorcontrib><creatorcontrib>Moestue, Siver Andreas</creatorcontrib><creatorcontrib>Kim, Jana</creatorcontrib><creatorcontrib>Nonstad, Unni</creatorcontrib><creatorcontrib>Romundstad, Pål Richard</creatorcontrib><creatorcontrib>Skorpen, Frank</creatorcontrib><creatorcontrib>Sørhaug, Sveinung</creatorcontrib><creatorcontrib>Amundsen, Tore</creatorcontrib><creatorcontrib>Grønberg, Bjørn Henning</creatorcontrib><creatorcontrib>Strasser, Florian</creatorcontrib><creatorcontrib>Stephens, Nathan</creatorcontrib><creatorcontrib>Hoem, Dag</creatorcontrib><creatorcontrib>Molven, Anders</creatorcontrib><creatorcontrib>Kaasa, Stein</creatorcontrib><creatorcontrib>Fearon, Kenneth</creatorcontrib><creatorcontrib>Jacobi, Carsten</creatorcontrib><creatorcontrib>Bjørkøy, Geir</creatorcontrib><title>Cancer cachexia associates with a systemic autophagy-inducing activity mimicked by cancer cell-derived IL-6 trans-signaling</title><description>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 autophagyinducing 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. 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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 autophagyinducing 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.</abstract><pub>Nature Publishing Group</pub><oa>free_for_read</oa></addata></record> |
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title | Cancer cachexia associates with a systemic autophagy-inducing activity mimicked by cancer cell-derived IL-6 trans-signaling |
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