Journal article
Targeting of Fn14 Prevents Cancer-Induced Cachexia and Prolongs Survival
AJ Johnston, KT Murphy, L Jenkinson, D Laine, K Emmrich, P Faou, R Weston, KM Jayatilleke, J Schloegel, G Talbo, JL Casey, V Levina, WWL Wong, H Dillon, T Sahay, J Hoogenraad, H Anderton, C Hall, P Schneider, M Tanzer Show all
Cell | Published : 2015
Abstract
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 wou..
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Awarded by National Health and Medical Research Council
Funding Acknowledgements
We acknowledge financial support from the Cooperative Research Centre for Biomarker Translation and the NHMRC. We thank Timur Naim, Annabel Chee, and Jennifer Trieu for expert technical assistance. We acknowledge the provision of the activin construct, AAV vectors, and technical assistance by Craig Harrison, Hongwei Qian, and Justin Chen. We also acknowledge Stephen Wilcox for MEF tumor cell line genome DNA sequencing. J. Silke is supported by NHMRC grants #541901 and 1058190. K.T.M. is supported by an NHMRC Career Development Fellowship. P.S. is supported by Swiss National Science Foundation grants. N.J.H., J. Silke, and A.M.S. are supported by an NHMRC Development Grant #1075504. L.C.B. is an employee and stockholder of Biogen, Inc.