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- Title
Upregulation of IL-11, an IL-6 Family Cytokine, Promotes Tumor Progression and Correlates with Poor Prognosis in Non-Small Cell Lung Cancer.
- Authors
Zhao, Meng; Liu, Yahui; Liu, Ran; Qi, Jin; Hou, Yongwang; Chang, Jiao; Ren, Li
- Abstract
<bold><italic>Background/Aims:</italic></bold> 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. <bold><italic>Methods:</italic></bold> 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 <italic>in vivo</italic>. 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. <bold><italic>Results:</italic></bold> We observed that IL-11 was upregulated in NSCLC samples compared with normal tissue samples and correlated with poor prognosis. Data from <italic>in vitro</italic> and <italic>in vivo</italic> 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 (HIF1α) upregulation, which enhanced IL-11 expression in NSCLC cells. <bold><italic>Conclusions</italic></bold><bold><italic>:</italic></bold> 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.
- Subjects
THERAPEUTIC use of cytokines; INTERLEUKIN-11; CANCER invasiveness; NON-small-cell lung carcinoma; NEOPLASTIC cell transformation
- Publication
Cellular Physiology & Biochemistry (Karger AG), 2018, Vol 45, Issue 6, p2213
- ISSN
1015-8987
- Publication type
Article
- DOI
10.1159/000488166