Journal article
A dynamic inflammatory cytokine network in the human ovarian cancer microenvironment
H Kulbe, P Chakravarty, DA Leinster, KA Charles, J Kwong, RG Thompson, JI Coward, T Schioppa, SC Robinson, WM Gallagher, L Galletta, MA Salako, JF Smyth, T Hagemann, DJ Brennan, DD Bowtell, FR Balkwill
Cancer Research | Published : 2012
Abstract
Constitutive production of inflammatory cytokines is a characteristic of many human malignant cell lines; however, the in vitro and in vivo interdependence of these cytokines, and their significance to the human cancer microenvironment, are both poorly understood. Here, we describe for the first time how three key cytokine/chemokine mediators of cancer-related inflammation, TNF, CXCL12, and interleukin 6, are involved in an autocrine cytokine network, the "TNF network," in human ovarian cancer. We show that this network has paracrine actions on angiogenesis, infiltration of myeloid cells, and NOTCH signaling in both murine xenografts and human ovarian tumor biopsies. Neutralizing antibodies ..
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Awarded by Medical Research Council
Funding Acknowledgements
H. Kulbe, T. Schioppa, P. Chakravarty were funded by Cancer Research United Kingdom; J. Kwong was funded by AICR; D. A. Leinster and J. Kwong were funded by MRC; S. C. Robinson was funded by Barts and the London Charity, M. A. Salako was funded by Ovarian Cancer Action; T. Hagemann was funded by the MRC; R. G. Thompson and F. R. Balkwill were funded by HEFCE; and D. D. Bowtell is funded by the National Health and Medical Research Council of Australia, Cancer Councils of Australia, and the US Department of Defense Ovarian Cancer Research Program. The UCD Conway Institute is funded by the PRTLI administered by the Higher Education Authority of Ireland.