Targeting of Fn14 prevents cancer-induced cachexia and prolongs survival

Amelia J. Johnston, Kate T. Murphy, Laura Jenkinson, David Laine, Kerstin Emmrich, Pierre Faou, Ross Weston, Krishnath M. Jayatilleke, Jessie Schloegel, Gert Talbo, Joanne L. Casey, Vita Levina, W. Wei-Lynn Wong, Helen Dillon, Tushar Sahay, Joan Hoogenraad, Holly Anderton, Cathrine Hall, Pascal Schneider, Maria TanzerMichael Foley, Andrew M. Scott, Paul Gregorevic, Spring Yingchun Liu, Linda C. Burkly, Gordon S. Lynch, John Silke, Nicholas J. Hoogenraad

Research output: Contribution to journalArticleResearchpeer-review

105 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)1365-1378
Number of pages14
JournalCell
Volume162
Issue number6
DOIs
Publication statusPublished - 10 Sept 2015

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