Details

Autor(en) / Beteiligte

• Numasaki, Muneo
• Fukushi, Jun-ichi
• Ono, Mayumi
• Narula, Satwant K.
• Zavodny, Paul J.
• Kudo, Toshio
• Robbins, Paul D.
• Tahara, Hideaki
• Lotze, Michael T.

Titel

Interleukin-17 promotes angiogenesis and tumor growth

Ist Teil von

• Blood, 2003-04, Vol.101 (7), p.2620-2627

Ort / Verlag

Washington, DC: Elsevier Inc

Erscheinungsjahr

2003

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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-17gene 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.