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

本研究探讨了IL-26对人非小细胞肺癌(NSCLC)的生物学作用。IL-26对NSCLC的体外生长无直接影响，但IL-26通过两种不同的NSCLC株选择性地促进CXCL1、CXCL5、CXCL6和CXCL8等一系列血管生成的CXC趋化因子的分泌，但不促进血管抑制性趋化因子的分泌。IL-26基因转染对NSCLC的体外生长无明显影响，而IL-26基因在SCID小鼠体内的生长速度明显快于对照组。这种IL-26诱导的NSCLC生长增强与肿瘤血管的增加有关。此外，抗小鼠CXCR-2中和抗体显著抑制了新基因和IL-26基因转导的SCID小鼠NSCLC肿瘤的生长。这些结果表明，IL-26通过促进CXCR-2依赖的血管生成增加NSCLC的净血管生成活性和体内生长，提示靶向CXCR-2信号转导可能是治疗NSCLC的一种新的有前途的策略。

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.