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Prepublished online as a Blood First Edition Paper on October 31, 2002; DOI 10.1182/blood-2002-05-1461. This Article Full Text (PDF) All Versions of this Article: 2002-05-1461v1 101/7/2620    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Numasaki, M. Articles by Lotze, M. T Search for Related Content PubMed PubMed Citation Articles by Numasaki, M. Articles by Lotze, M. T Social Bookmarking                   What's this? Submitted May 20, 2002 Accepted October 8, 2002 Interleukin-17 promotes angiogenesis and tumor growth Muneo Numasaki*, Jun-ichi Fukushi, Mayumi Ono, Satwant K Narula, Paul J Zavodny, Toshio Kudo, Paul D Robbins, Hideaki Tahara, and Michael T Lotze Department of Surgery, School of Medicine, University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA, USA Department of Molecular Genetics and Biochemistry, School of Medicine, University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA, USA Department of Geriatic and Respiratory Medicine, Tohoku University School of Medicine, Sendai, Japan Department of Medical Biochemistry, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan Department of Immunology, Schering-Plough Research Institute, Kenilworth, NJ, USA Cell Resource Center for Biomedical Research, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan * Corresponding author; email: numasaki77{at}aol.com. Interleukin-17 (IL-17) is a CD4 T cell-derived proinflammatory cytokine. We investigated the effects of locally produced IL-17 by tumors as a means to evaluate its biological function. While recombinant IL-17 protein or retroviral transduction of IL-17 gene into tumors did not affect in vitro proliferation, IL-17 transfectants grew more rapidly in vivo when compared with controls. Immunostaining with Factor VIII revealed that tumors transduced with IL-17 had significantly higher vascular density compared with controls. IL-17 indeed elicited neovascularization in rat cornea. In addition, angiogenic activity present in the conditioned media of CD4 T cells was markedly suppressed by neutralizing mAb to IL-17. IL-17 had no direct effect on the growth of vascular endothelial cells, whereas IL-17 significantly stimulated migration. IL-17 also markedly promoted the cord formation of vascular endothelial cells. In addition, IL-17 upregulated elaboration of a variety of proangiogenic factors by fibroblasts as well as tumor cells, that was further enhanced by macrophage-derived cytokine tumor necrosis factor (TNF)-. These findings reveal a novel role for IL-17 as a CD4 T cell-derived mediator of angiogenesis that stimulates vascular endothelial cell migration and cord formation and regulates production of a variety of proangiogenic factors, and futhermore suggest that inhibition of biological action of IL-17 may have therapeutic benefits when applied to angiogenesis-related disorders. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. D. Sharma, S. M. Meeran, N. Katiyar, G. B. Tisdale, N. Yusuf, H. Xu, C. A. Elmets, and S. K. 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