Interleukin-17 promotes angiogenesis and tumor growth

M Numasaki, J Fukushi, M Ono… - Blood, The Journal …, 2003 - ashpublications.org
M Numasaki, J Fukushi, M Ono, SK Narula, PJ Zavodny, T Kudo, PD Robbins, H Tahara…
Blood, The Journal of the American Society of Hematology, 2003ashpublications.org
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 …
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 ofIL-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.
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