Targeting of Fn14 Prevents Cancer-Induced Cachexia and Prolongs Survival.


Autoria(s): Johnston A.J.; Murphy K.T.; Jenkinson L.; Laine D.; Emmrich K.; Faou P.; Weston R.; Jayatilleke K.M.; Schloegel J.; Talbo G.; Casey J.L.; Levina V.; Wong W.W.; Dillon H.; Sahay T.; Hoogenraad J.; Anderton H.; Hall C.; Schneider P.; Tanzer M.; Foley M.; Scott A.M.; Gregorevic P.; Liu S.Y.; Burkly L.C.; Lynch G.S.; Silke J.; Hoogenraad N.J.
Data(s)

2015

Resumo

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.

Identificador

http://serval.unil.ch/?id=serval:BIB_315D44A92CD8

isbn:1097-4172 (Electronic)

pmid:26359988

doi:10.1016/j.cell.2015.08.031

isiid:000361247900024

Idioma(s)

en

Fonte

Cell, vol. 162, no. 6, pp. 1365-1378

Tipo

info:eu-repo/semantics/article

article