Key Laboratory for Experimental Teratology of Ministry of Education and Department of Immunology, Shandong Provincial Key Laboratory of Infection & Immunology, School of Basic Medical Sciences, Shandong University, Jinan, Shandong, China.
Laboratory for Tissue Engineering and Regeneration, School of Stomatology, Shandong University, Jinan, Shandong, China.
Cell Prolif. 2020 Mar;53(3):e12776. doi: 10.1111/cpr.12776. Epub 2020 Feb 5.
Interleukin-6 (IL-6) is critical for the development of non-small-cell lung cancer (NSCLC). Recently, we identified T-cell immunoglobulin domain and mucin domain 4 (TIM-4) as a new pro-growth player in NSCLC progression. However, the role of TIM-4 in IL-6-promoted NSCLC migration, invasion and epithelial-to-mesenchymal transition (EMT) remains unclear.
Expressions of TIM-4 and IL-6 were both evaluated by immunohistochemical staining in NSCLC tissues. Real-time quantitative PCR (qPCR), Western blot, flow cytometry and RT-PCR were performed to detect TIM-4 expression in NSCLC cells with IL-6 stimulation. The roles of TIM-4 in IL-6 promoting migration and invasion of NSCLC were detected by transwell assay. EMT-related markers were analysed by qPCR and Western blot in vitro, and metastasis was evaluated in BALB/c nude mice using lung cancer metastasis mouse model in vivo.
High IL-6 expression was identified as an independent predictive factor for TIM-4 expression in NSCLC tissues. NSCLC patients with TIM-4 and IL-6 double high expression showed the worst prognosis. IL-6 promoted TIM-4 expression in NSCLC cells depending on NF-κB signal pathway. Both TIM-4 and IL-6 promoted migration, invasion and EMT of NSCLC cells. Interestingly, TIM-4 knockdown reversed the role of IL-6 in NSCLC and IL-6 promoted metastasis of NSCLC by up-regulating TIM-4 via NF-κB.
TIM-4 involves in IL-6 promoted migration, invasion and EMT of NSCLC.
白细胞介素 6（IL-6）对于非小细胞肺癌（NSCLC）的发展至关重要。最近，我们发现 T 细胞免疫球蛋白结构域和粘蛋白结构域 4（TIM-4）是 NSCLC 进展中一种新的促生长因子。然而，TIM-4 在 IL-6 促进 NSCLC 迁移、侵袭和上皮间质转化（EMT）中的作用尚不清楚。
采用免疫组织化学染色法检测 NSCLC 组织中 TIM-4 和 IL-6 的表达。采用实时定量 PCR（qPCR）、Western blot、流式细胞术和 RT-PCR 检测 IL-6 刺激下 NSCLC 细胞中 TIM-4 的表达。通过 Transwell 实验检测 TIM-4 在 IL-6 促进 NSCLC 迁移和侵袭中的作用。体外通过 qPCR 和 Western blot 分析 EMT 相关标志物，体内采用 NSCLC 转移小鼠模型在 BALB/c 裸鼠中评估转移。
高 IL-6 表达被鉴定为 NSCLC 组织中 TIM-4 表达的独立预测因子。TIM-4 和 IL-6 双高表达的 NSCLC 患者预后最差。IL-6 通过 NF-κB 信号通路促进 NSCLC 细胞中 TIM-4 的表达。TIM-4 和 IL-6 均促进 NSCLC 细胞的迁移、侵袭和 EMT。有趣的是，TIM-4 敲低逆转了 IL-6 在 NSCLC 中的作用，而 IL-6 通过 NF-κB 上调 TIM-4 促进了 NSCLC 的转移。
TIM-4 参与了 IL-6 促进的 NSCLC 迁移、侵袭和 EMT。
