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Interleukin-17 promotes angiogenesis and tumor growth

Academic Article
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Overview

authors

  • Numasaki, M.
  • Fukushi, J.
  • Ono, M.
  • Narula, S. K.
  • Zavodny, P. J.
  • Kudo, T.
  • Robbins, Paul D.
  • Tahara, H.
  • Lotze, M. T.

publication date

  • April 2003

journal

  • Blood  Journal

abstract

  • 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.

subject areas

  • Animals
  • Cell Division
  • Chemotaxis
  • Cornea
  • Endothelium, Vascular
  • Female
  • Growth Substances
  • Humans
  • Interleukin-17
  • Mice
  • Mice, Inbred C57BL
  • Neoplasms, Experimental
  • Neovascularization, Pathologic
  • Rats
  • Transduction, Genetic
  • Umbilical Veins
  • Up-Regulation
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Identity

International Standard Serial Number (ISSN)

  • 0006-4971

Digital Object Identifier (DOI)

  • 10.1182/blood-2002-05-1461

PubMed ID

  • 12411307
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Additional Document Info

start page

  • 2620

end page

  • 2627

volume

  • 101

issue

  • 7

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