| Project/Area Number |
15590791
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Respiratory organ internal medicine
|
|---|
| Research Institution | Tohoku University |
|---|
Principal Investigator |
NUMASAKI Muneo Tohoku University, Hospital, Research Associate, 病院, 助手 (50344677)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
KUBO Hiroshi Tohoku University, Hospital, Research Associate, 病院・助手 (20332504)
|
|---|
| Project Period (FY) |
2003 – 2004
|
| Project Status |
Completed (Fiscal Year 2004)
|
| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2004: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2003: ¥1,700,000 (Direct Cost: ¥1,700,000)
|
|---|
| Keywords | Lung Cancer / Cytokine / Angiogenesis / 血管新生因子 |
|---|
| 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.
|
