Upregulation of IL-11,an IL-6 Family Cytokine, Promotes Tumor Progression and Correlates with Poor Prognosis in Non-Small Cell Lung Cancer
Upregulation of IL-11,an IL-6 Family Cytokine, Promotes Tumor Progression and Correlates with Poor Prognosis in Non-Small Cell Lung Cancer
复制标题
IL-11（一种 IL-6 家族细胞因子）的上调可促进肿瘤进展并与非小细胞肺癌的不良预后相关。
DOI：
10.1159/000488166
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发表时间：
2018-01-01
影响因子：
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通讯作者：
Ren, Li
中科院分区：
文献类型：
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作者：
Zhao, Meng;Liu, Yahui;Ren, Li
背景/目的：细胞因子是肿瘤发生的关键参与者，也是癌症治疗的潜在靶点。虽然IL-6引起了人们的广泛关注，但IL-6家族的另一个成员白细胞介素11（IL-11）长期以来一直被忽视，并且对其在非小细胞肺癌（NSCLC）中的特异性功能知之甚少。方法：采用集落形成法、BrdU掺入法和MTS（3-（4，5-dimethylthiazol-2- yl）-5-（3-carboxymethoxyphenyl）-2-（4-sulfophenyl）-2 H-tetrazolium）法检测IL-11对NSCLC细胞增殖的影响。通过Transwell和伤口愈合测定来测量细胞运动性。NSCLC异种移植模型用于确认IL-11在体内的致癌功能。采用免疫组化和Western blot方法检测上皮-间质转化（EMT）标志物和细胞信号通路的改变。收集了18例NSCLC患者和5例正常肺样本以及来自在线数据库的数据，以确定IL-11表达与恶性进展之间的联系。结果：我们观察到IL-11在NSCLC样品中比正常组织样品上调，并且与不良预后相关。来自体外和体内模型的数据表明，IL-11促进细胞增殖和肿瘤发生。IL-11还增强了细胞的迁移和侵袭。IL-11孵育后还观察到上皮-间质转化（EMT）。此外，在我们的实验模型中，IL-11激活AKT和STAT 3。此外，我们观察到低氧诱导NSCLC细胞中IL-11的表达。去铁胺（DFX）或二甲基草酰甘氨酸（DMOG）诱导低氧诱导因子1-α（HIF 1 α）上调，这增强了NSCLC细胞中IL-11的表达。结论：综上所述，我们的结果表明IL-11是NSCLC中的癌基因，阐明其背后的机制可能为NSCLC治疗提供见解。(C)2018作者（S）由S发布。Karger AG，巴塞尔
Background/Aims: Cytokines are key players in tumorigenesis and are potential targets in cancer treatment. Although IL-6 has attracted considerable attention, interleukin 11 (IL-11), another member of the IL-6 family, has long been overlooked, and little is known regarding its specific function in non-small cell lung cancer (NSCLC). In this study, we explored IL-11's role in NSCLC and the detailed mechanism behind it. Methods: Cell proliferation in response to IL-11 was determined by colony formation, BrdU incorporation and MTS (3-(4,5-dimethylthiazol-2- yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assay. Cell motility was measured by Transwell and wound healing assays. NSCLC xenograft models were used to confirm oncogenic function of IL-11 in vivo. Immunohistochemical staining and western blot assay were performed to detect epithelial-mesenchymal transition (EMT) markers and cell signaling pathway alterations. Eighteen NSCLC patients and 5 normal lung samples were collected together with data from an online database to determine the link between IL-11 expression and malignant progression. Results: We observed that IL-11 was upregulated in NSCLC samples compared with normal tissue samples and correlated with poor prognosis. Data from in vitro and in vivo models indicated that IL-11 promotes cell proliferation and tumorigenesis. Cell migration and invasion were also enhanced by IL-11. Epithelial-mesenchymal transition (EMT) was also observed after IL-11 incubation. Furthermore, IL-11 activated AKT and STAT3 in our experimental models. In addition, we observed that hypoxia induced IL-11 expression in NSCLC cells. Deferoxamine (DFX) or dimethyloxalylglycine (DMOG) induced hypoxia-inducible factor 1-alpha (HIF1 alpha) upregulation, which enhanced IL-11 expression in NSCLC cells. Conclusions: Taken together, our results indicate that IL-11 is an oncogene in NSCLC, and elucidating the mechanism behind it may provide insights for NSCLC treatment. (C) 2018 The Author(s) Published by S. Karger AG, Basel