Targeting of Fn14 Prevents Cancer-Induced Cachexia and Prolongs Survival.
Details
Download: JOhnston2015.pdf (2552.35 [Ko])
State: Public
Version: Author's accepted manuscript
State: Public
Version: Author's accepted manuscript
Serval ID
serval:BIB_315D44A92CD8
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Targeting of Fn14 Prevents Cancer-Induced Cachexia and Prolongs Survival.
Journal
Cell
ISSN
1097-4172 (Electronic)
ISSN-L
0092-8674
Publication state
Published
Issued date
2015
Volume
162
Number
6
Pages
1365-1378
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Publication Status: ppublish
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.
Pubmed
Web of science
Open Access
Yes
Create date
09/10/2015 8:08
Last modification date
20/08/2019 14:16