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, Michael T. Lotze

Research output: Contribution to journalArticlepeer-review

727 Scopus citations


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. Furthermore, they suggest that inhibition of biologic action of IL-17 may have therapeutic benefits when applied to angiogenesis-related disorders.

Original languageEnglish (US)
Pages (from-to)2620-2627
Number of pages8
Issue number7
StatePublished - Apr 1 2003
Externally publishedYes


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