Targeting of Fn14 prevents cancer-induced cachexia and prolongs survival
Details
Publication Year 2015-09-10, Volume 162, Issue #6, Page 1365-78
Journal Title
Cell
Publication Type
Journal Article
Abstract
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.
Publisher
Cell Press
WEHI Research Division(s)
Cell Signalling And Cell Death
PubMed ID
26359988
NHMRC Grants
NHMRC/541901 NHMRC/1058190 NHMRC/1075504
Rights Notice
Refer to copyright notice on published article.


Creation Date: 2015-09-24 02:12:25
Last Modified: 2016-03-30 03:28:34
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