2004 Fiscal Year Final Research Report Summary
Investigation of the role for novel angiogenic factor IL-17 in human non-small cell lung cancer-induced tumor angiogenesis
| Project/Area Number |
15590791
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | Tohoku University |
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Principal Investigator |
NUMASAKI Muneo Tohoku University, Hospital, Research Associate, 病院, 助手 (50344677)
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| Co-Investigator(Kenkyū-buntansha) |
KUBO Hiroshi Tohoku University, Hospital, Research Associate, 病院・助手 (20332504)
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| Project Period (FY) |
2003 – 2004
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| Keywords | Lung Cancer / Cytokine / Angiogenesis |
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| Research Abstract |
In this study, we examined the biological action of IL-17 on human non-small cell lung cancer (NSCLC). While IL-17 had no direct effect on the in vitro growth rate of NSCLC, IL-17 selectively augmented the secretion of an array of angiogenic CXC chemokines including CXCL1, CXCL5, CXCL6 and CXCL8, but not angiostatic chemokines, by three NSCLC lines. Endothelial cell chemotactic activity (as a measure of net angiogenic potential) was increased in response to conditioned media from NSCLC stimulated with IL-17 compared with those from unstimulated NSCLC. Enhanced chemotactic activity was suppressed by neutralizing mAb(s) to CXCL1 CXCL5 and CXCL8 or to CXCR-2, but not to VEGF. Transfection with IL-17 into NSCLC had no effect on the in vitro growth, whereas IL-17 transfectants grew more rapidly compared with controls when transplanted in SCID mice. This IL-17-elicited enhanced NSCLC growth was associated with increased tumor vascularity. Moreover, treatment with anti-mouse CXCR-2 neutralizing Ab significantly attenuated the growth of both Neo-and IL-17-transfected NSCLC tumors in SCID mice. A potential role for IL-17 in modulation of the human NSCLC phenotype was supported by the findings that, in primary NSCLC tissues, IL-17 expression was frequently detected only in accumulating and infiltrating inflammatory cells and high levels of IL-17 expression were associated with increased vascularity. These results demonstrate that IL-17 increases the net angiogenic activity and in vivo growth of NSCLC via promoting CXCR-2-dependent angiogenesis and suggest that targeting CXCR-2 signaling may be a novel promising strategy to treat patients with NSCLC.
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Research Products
(4 results)
