title: Interleukin-17 promotes angiogenesis and tumor growth.
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.
authors.affiliation: Department of Surgery, School of Medicine, University of Pittsburgh Cancer Institute, University of Pittsburgh, PA, USA. numasaki77@aol.com
authors.forename: Muneo
authors.initials: M
authors.lastname: Numasaki
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Fukushi
authors.forename: Mayumi
authors.initials: M
authors.lastname: Ono
authors.forename: Satwant K
authors.initials: SK
authors.lastname: Narula
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Zavodny
authors.forename: Toshio
authors.initials: T
authors.lastname: Kudo
authors.forename: Paul D
authors.initials: PD
authors.lastname: Robbins
authors.forename: Hideaki
authors.initials: H
authors.lastname: Tahara
authors.forename: Michael T
authors.initials: MT
authors.lastname: Lotze
mesh_terms: D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002633:Chemotaxis / Q000187:drug effects; D003315:Cornea / Q000098:blood supply / Q000187:drug effects; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D005260:Female; D006133:Growth Substances / Q000096:biosynthesis; D006801:Humans; D020381:Interleukin-17 / Q000235:genetics / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000209:etiology / Q000473:pathology*; D009389:Neovascularization, Pathologic / Q000139:chemically induced*; D051381:Rats; D014161:Transduction, Genetic; D014471:Umbilical Veins / Q000166:cytology; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D006133:Growth Substances; D020381:Interleukin-17