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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 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 Citation Map 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. Related Collections Hemostasis, Thrombosis, and Vascular Biology Immunobiology Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 April 2003, Vol. 101, No. 7, pp. 2620-2627 HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY 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 From the Departments of Surgery and Molecular Genetics and Biochemistry, School of Medicine, University of Pittsburgh Cancer Institute, University of Pittsburgh, PA; Department of Geriatric 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; Cell Resource Center for Biomedical Research, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan. 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 biologic function. Although 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 for Factor VIII revealed that tumors transduced with IL-17 had significantly higher vascular density when 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 monoclonal antibody 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 up-regulated elaboration of a variety of proangiogenic factors by fibroblasts as well as tumor cells. 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. 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