Promotion of a cancer-like phenotype, through chronic exposure to inflammatory cytokines and hypoxia in a bronchial epithelial cell line model.
Promotion of a cancer-like phenotype, through chronic exposure to inflammatory cytokines and hypoxia in a bronchial epithelial cell line model.
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DOI：
10.1038/srep18907
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发表时间：
2016-01-13
影响因子：
4.6
通讯作者：
O'Byrne KJ
中科院分区：
文献类型：
--
作者：
Baird AM;Gray SG;Richard DJ;O'Byrne KJ
在全球范围内，肺癌约占所有与癌症相关的死亡人数的20%。五年存活率很低，过去40年来利率一直保持不变。迫切需要确定肺癌发生的标记物和新的治疗靶点。鉴于最近免疫调节剂在癌症治疗中的成功以及对肿瘤免疫逃逸的更好理解，我们试图在正常的支气管上皮细胞系模型中确定慢性肿瘤坏死因子-α和白介素1β暴露的致癌影响。在常氧和低氧(0.5%氧气)条件下，在慢性炎症环境中培养三个月后，正常细胞发生了一些关键的基因和表型变化。重要的细胞特征，如正常细胞的增殖、黏附和侵袭能力显著增强。此外，在与细胞凋亡、血管生成和侵袭相关的途径中，基因表达谱也发生了变化。这项研究中产生的数据支持肿瘤坏死因子-α、白介素1β和低氧促进正常支气管上皮细胞的肿瘤表型。反过来，这些介质可能对生物标记物和/或免疫治疗靶标研究有利。该项目为肺癌免疫肿瘤学的进一步研究提供了重要的体外炎症模型。
Globally, lung cancer accounts for approximately 20% of all cancer related deaths. Five-year survival is poor and rates have remained unchanged for the past four decades. There is an urgent need to identify markers of lung carcinogenesis and new targets for therapy. Given the recent successes of immune modulators in cancer therapy and the improved understanding of immune evasion by tumours, we sought to determine the carcinogenic impact of chronic TNF-α and IL-1β exposure in a normal bronchial epithelial cell line model. Following three months of culture in a chronic inflammatory environment under conditions of normoxia and hypoxia (0.5% oxygen), normal cells developed a number of key genotypic and phenotypic alterations. Important cellular features such as the proliferative, adhesive and invasive capacity of the normal cells were significantly amplified. In addition, gene expression profiles were altered in pathways associated with apoptosis, angiogenesis and invasion. The data generated in this study provides support that TNF-α, IL-1β and hypoxia promotes a neoplastic phenotype in normal bronchial epithelial cells. In turn these mediators may be of benefit for biomarker and/or immune-therapy target studies. This project provides an important inflammatory in vitro model for further immuno-oncology studies in the lung cancer setting.