Cell
Volume 162, Issue 6, 10 September 2015, Pages 1365-1378
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Article
Targeting of Fn14 Prevents Cancer-Induced Cachexia and Prolongs Survival

https://doi.org/10.1016/j.cell.2015.08.031Get rights and content
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Highlights

  • Tumors expressing Fn14 cause cachexia in mice

  • Fn14 antibodies extend lifespan by inhibiting tumor-induced cachexia

  • Fn14- and TWEAK-deficient mice succumb to cancer cachexia

  • Tumor Fn14 signaling, rather than host, is responsible for inducing cachexia

Summary

The cytokine TWEAK and its cognate receptor Fn14 are members of the TNF/TNFR superfamily and are upregulated in tumors. We found that Fn14, when expressed in tumors, causes cachexia and that antibodies against Fn14 dramatically extended lifespan by inhibiting tumor-induced weight loss although having only moderate inhibitory effects on tumor growth. Anti-Fn14 antibodies prevented tumor-induced inflammation and loss of fat and muscle mass. Fn14 signaling in the tumor, rather than host, is responsible for inducing this cachexia because tumors in Fn14- and TWEAK-deficient hosts developed cachexia that was comparable to that of wild-type mice. These results extend the role of Fn14 in wound repair and muscle development to involvement in the etiology of cachexia and indicate that Fn14 antibodies may be a promising approach to treat cachexia, thereby extending lifespan and improving quality of life for cancer patients.

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