METHODS: Immunohistochemistry was utilized to assess the differential expression levels of IL-17A and CXCL12 in tumor versus normal tissues of LUAD patients, followed by gene correlation analysis. Cell counting kit-8 (CCK8), wound-healing and transwell assays were performed to investigate the effect of IL-17A on the function of LUAD cells. qPCR, immunofluorescence, immunohistochemistry and western blot analyses were conducted to elucidate the potential mechanism by which IL-17A facilitates the development of LUAD via CXCL12. Male BALB-C nude mice were used to explore the role of IL-17A in subcutaneous LUAD mouse models.
RESULTS: Elevated expression levels of IL-17A and CXCL12 were observed in LUAD tissues, exhibiting a positive correlation. Further studies revealed that IL-17A could stimulate CAFs to enhance the release of CXCL12, thereby facilitating the growth, proliferation, and metastasis of LUAD. The binding of CXCL12 to its specific receptor influences the activation of the Wnt/β-Catenin pathway, which in turn affects the progression of LUAD. In vivo experiments have demonstrated that IL-17A enhances the growth of LUAD tumors by facilitating the secretion of CXCL12. Conversely, inhibiting CXCL12 has been demonstrated to impede tumor growth.
CONCLUSIONS: We discovered that IL-17A promotes the release of CAFs-derived CXCL12, which in turn facilitates the development of LUAD via the Wnt/β-Catenin signaling pathway.
方法:免疫组织化学用于评估LUAD患者肿瘤与正常组织中IL-17A和CXCL12的差异表达水平,然后进行基因相关性分析。细胞计数试剂盒-8(CCK8),进行伤口愈合和transwell测定以研究IL-17A对LUAD细胞功能的影响。qPCR,免疫荧光,进行了免疫组织化学和蛋白质印迹分析,以阐明IL-17A通过CXCL12促进LUAD发展的潜在机制.用雄性BALB-C裸鼠探讨IL-17A在皮下LUAD小鼠模型中的作用。
结果:在LUAD组织中观察到IL-17A和CXCL12的表达水平升高,表现出正相关。进一步的研究表明,IL-17A可以刺激CAFs增强CXCL12的释放,从而促进其生长,扩散,和LUAD的转移。CXCL12与其特异性受体的结合影响Wnt/β-Catenin通路的激活,进而影响LUAD的进展。体内实验已经证明IL-17A通过促进CXCL12的分泌来增强LUAD肿瘤的生长。相反,已经证明抑制CXCL12阻碍肿瘤生长。
结论:我们发现IL-17A促进CAFs来源的CXCL12的释放,进而通过Wnt/β-Catenin信号通路促进LUAD的发展。