Novel treatment of non-small cell lung cancer with the inhibition of IL-26-induced tumor angiogenesis

通过抑制 IL-26 诱导的肿瘤血管生成治疗非小细胞肺癌

• 批准号: 17590775
• 负责人: NUMASAKI Muneo
• 金额: $ 2.3万
• 依托单位: TOHOKU UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17590775/
• 关键词: angiogenesis; cytokine; non-small cell lung cancer; 肺癌

In this study, we examined the biological action of IL-26 on human non-small cell lung cancer (NSCLC). While IL-26 had no direct effect on the in vitro growth rate of NSCLC, IL-26 selectively augmented the secretion of an array of angiogenic CXC chemokines including CXCL1, CXCL5, CXCL6 and CXCL8, but not angiostatic chemokines, by two different NSCLC lines. Transfection with IL-26 into NSCLC had no effect on the in vitro growth, whereas IL-26 transfectants grew more rapidly compared with controls when transplanted in SCID mice. This IL-26-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-26-transfected NSCLC tumors in SCID mice. These results demonstrate that IL-26 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.

本研究旨在探讨IL-26对人非小细胞肺癌（NSCLC）的生物学作用。虽然IL-26对NSCLC的体外生长速率没有直接影响，但IL-26选择性地增加了两种不同NSCLC细胞系的一系列血管生成CXC趋化因子（包括CXCL 1、CXCL 5、CXCL 6和CXCL 8）的分泌，但不增加血管生成抑制趋化因子的分泌。用IL-26转染到NSCLC中对体外生长没有影响，而当移植到SCID小鼠中时，与对照相比，IL-26转染子生长更快。这种IL-26诱导的NSCLC生长增强与肿瘤血管分布增加相关。此外，用抗小鼠CXCR-2中和Ab治疗显著减弱了SCID小鼠中Neo和IL-26转染的NSCLC肿瘤的生长。这些结果表明，IL-26通过促进CXCR-2依赖性血管生成来增加NSCLC的净血管生成活性和体内生长，并且表明靶向CXCR-2信号传导可能是治疗NSCLC患者的新的有希望的策略。

项目成果

Interleukin-17 enhances bFGF-, HGF- and VEGF-induced growth of vascular endothelial cells

• DOI: 10.1016/j.imlet.2004.11.012
• 发表时间: 2005-05-15
• 期刊: IMMUNOLOGY LETTERS
• 影响因子: 4.4
• 作者: Takahashi, H;Numasaki, M;Sasaki, H
• 通讯作者: Sasaki, H

Mechanisms of mucin production by rhinovirus infection in cultured human airway epithelial cells

• DOI: 10.1016/j.resp.2005.11.006
• 发表时间: 2006-12-01
• 期刊: RESPIRATORY PHYSIOLOGY & NEUROBIOLOGY
• 影响因子: 2.3
• 作者: Inoue, Daisuke;Yamaya, Mutsuo;Sasaki, Hidetada
• 通讯作者: Sasaki, Hidetada

IL-17 enhances the net angiogenic activity and in vivo growth of human non-small cell lung cancer in SCID mice through promoting CXCR-2-dependent angiogenesis

• DOI: 10.4049/jimmunol.175.9.6177
• 发表时间: 2005-11-01
• 期刊: JOURNAL OF IMMUNOLOGY
• 影响因子: 4.4
• 作者: Numasaki, M;Watanabe, M;Sasaki, H
• 通讯作者: Sasaki, H

IL-17A promotes the growth of airway epithelial cells through ERK-dependent signaling pathway

• DOI: 10.1016/j.bbrc.2006.06.137
• 发表时间: 2006-09-08
• 期刊: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
• 影响因子: 3.1
• 作者: Inoue, Daisuke;Numasaki, Muneo;Sasaki, Hidetada
• 通讯作者: Sasaki, Hidetada