Journal article
Interleukin-11 is the dominant Il-6 family cytokine during gastrointestinal tumorigenesis and can be targeted therapeutically
TL Putoczki, S Thiem, A Loving, RA Busuttil, NJ Wilson, PK Ziegler, PM Nguyen, A Preaudet, R Farid, KM Edwards, Y Boglev, RB Luwor, A Jarnicki, D Horst, A Boussioutas, JK Heath, OM Sieber, I Pleines, BT Kile, A Nash Show all
Cancer Cell | Published : 2013
Abstract
Among the cytokines linked to inflammation-associated cancer, interleukin (IL)-6 drives many of the cancer "hallmarks" through downstream activation of the gp130/STAT3 signaling pathway. However, we show that the related cytokine IL-11 has a stronger correlation with elevated STAT3 activation in human gastrointestinal cancers. Using genetic mouse models, we reveal that IL-11 has a more prominent role compared to IL-6 during the progression of sporadic and inflammation-associated colon and gastric cancers. Accordingly, in these models and in human tumor cell line xenograft models, pharmacologic inhibition of IL-11 signaling alleviated STAT3 activation, suppressed tumor cell proliferation, and..
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Awarded by European Commission
Funding Acknowledgements
We thank R. Hughan, C. Dijkstra, C. Nowell, J. Corbin, and the LICR Animal Facility and Histology staff for excellent technical assistance. We thank A. Strasser, T. Rowe, M. Griffin, and B. Klopcic for critical review of the manuscript and P. Waring and M. Christie for pathological assessment of the mouse and human histology, respectively. A cohort of the de-identified human GC tissue was provided by the Victorian Cancer Biobank. This work was made possible through Victorian State Government Operational Infrastructure Support and Australian Government NHMRC project grant 1008614 and program grants 487922 and 1016647. T.L.P. also received funding from the Cancer Australia priority driven research scheme, Cure Cancer Australia grant 603121. P.K.Z. was supported by a doctoral fellowship from the Deutsche Krebshilfe (110114). M.E., B.T.K., and J.K.H. are Senior Research Fellows of the NHMRC. N.J.W., K.M.E., A.N., and B.S.M. are employees of CSL, Ltd., and T.L.P. and M.E. received research support from CSL, Ltd.