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 journalArticle

599 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2620-2627
Number of pages8
JournalBlood
Volume101
Issue number7
DOIs
Publication statusPublished - Apr 1 2003
Externally publishedYes

Fingerprint

Interleukin-17
Tumors
Growth
Neoplasms
T-cells
Endothelial cells
Endothelial Cells
T-Lymphocytes
Factor VIII
Fibroblasts
Conditioned Culture Medium
Neutralizing Antibodies
Cornea
Cell Movement
Blood Vessels
Rats

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Numasaki, M., Fukushi, J-I., Ono, M., Narula, S. K., Zavodny, P. J., Kudo, T., ... Lotze, M. T. (2003). Interleukin-17 promotes angiogenesis and tumor growth. Blood, 101(7), 2620-2627. https://doi.org/10.1182/blood-2002-05-1461

Interleukin-17 promotes angiogenesis and tumor growth. / Numasaki, Muneo; Fukushi, Jun-Ichi; Ono, Mayumi; Narula, Satwant K.; Zavodny, Paul J.; Kudo, Toshio; Robbins, Paul D.; Tahara, Hideaki; Lotze, Michael T.

In: Blood, Vol. 101, No. 7, 01.04.2003, p. 2620-2627.

Research output: Contribution to journalArticle

Numasaki, M, Fukushi, J-I, Ono, M, Narula, SK, Zavodny, PJ, Kudo, T, Robbins, PD, Tahara, H & Lotze, MT 2003, 'Interleukin-17 promotes angiogenesis and tumor growth', Blood, vol. 101, no. 7, pp. 2620-2627. https://doi.org/10.1182/blood-2002-05-1461
Numasaki M, Fukushi J-I, Ono M, Narula SK, Zavodny PJ, Kudo T et al. Interleukin-17 promotes angiogenesis and tumor growth. Blood. 2003 Apr 1;101(7):2620-2627. https://doi.org/10.1182/blood-2002-05-1461
Numasaki, Muneo ; Fukushi, Jun-Ichi ; Ono, Mayumi ; Narula, Satwant K. ; Zavodny, Paul J. ; Kudo, Toshio ; Robbins, Paul D. ; Tahara, Hideaki ; Lotze, Michael T. / Interleukin-17 promotes angiogenesis and tumor growth. In: Blood. 2003 ; Vol. 101, No. 7. pp. 2620-2627.
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