Targeting of Fn14 Prevents Cancer-Induced Cachexia and Prolongs Survival.
Cell
; 162(6): 1365-78, 2015 Sep 10.
Article
in En
| MEDLINE
| ID: mdl-26359988
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cachexia
/
Receptors, Tumor Necrosis Factor
/
Neoplasms
Limits:
Animals
/
Female
/
Humans
Language:
En
Journal:
Cell
Year:
2015
Type:
Article