Epithelial-to-mesenchymal transition of A549 lung cancer cells exposed to electronic cigarettes.

Epithelial-to-mesenchymal transition of A549 lung cancer cells exposed to electronic cigarettes.
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暴露于电子卷烟的A549肺癌细胞的上皮到间质转变。

DOI:
10.1016/j.lungcan.2018.06.010
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发表时间:
2018-08
期刊:
Lung cancer (Amsterdam, Netherlands)
影响因子:
--
通讯作者:
Talbot P
Talbot P
中科院分区:
其他
文献类型:
--
作者:
Zahedi A;Phandthong R;Chaili A;Remark G;Talbot P

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上皮向间充质转化(EMT)是癌细胞转移的第一步,通常会导致死亡。尽管吸烟是肺癌的一个主要风险因素,但传统香烟的使用仍然很广泛。最近,电子烟(ECs)的引入改变了烟草行业的面貌,电子烟的致癌物质水平较低,可能提供一种更安全的替代品。在这里,我们研究EC液体和气雾剂在A549肺癌细胞中诱导EMT的能力。人肺泡腺癌A549细胞暴露于EC液和某流行产品的气雾剂中3-8天。使用活细胞成像、EMT生物标志物分析和机器学习/图像处理算法来表征与EMT相关的变化。A549细胞长期暴露在薄荷脑或烟草味EC液体或气雾剂中可诱导EMT,其特征是获得成纤维细胞样形态,细胞间连接丢失,E-钙粘蛋白内化,运动性增加,EMT标志物上调。EMT与活性β-连环蛋白的质膜向核转位是同步的。这是已知的第一项显示肺癌细胞在暴露于EC产品期间的EMT的研究。由于EMT是导致转移的第一步,这是一个经常导致患者死亡的棘手问题,这一关键发现对正在使用EC且可能有肺癌风险或可能已经患有肺癌的既往或重度吸烟者具有重大意义。
Epithelial-to-mesenchymal transition (EMT) is the initial step enabling the metastasis of cancer cells, which often leads to death. Although smoking is a major risk factor for lung cancer, there is still widespread use of conventional cigarettes. Recently, the tobacco industry has been transformed by the introduction of electronic cigarettes (ECs), which have lower levels of carcinogens and may provide a safer alternative. Here, we investigate the ability of EC liquids and aerosols to induce an EMT in A549 lung cancer cells. Human adenocarcinoma alveolar basal epithelial cells (A549) were exposed to EC liquids and aerosols from a popular product for 3–8 days. Live cell imaging, EMT biomarker analysis, and machine learning/image processing algorithms were used to characterize changes associated with EMT. Long-term exposure of A549 cells to menthol or tobacco-flavored EC liquids or aerosols induced an EMT that was characterized by acquisition of a fibroblast-like morphology, loss of cellto-cell junctions, internalization of E-cadherin, increased motility, and upregulation of EMT markers. The EMT was concurrent with plasma membrane to nuclear translocation of active β-catenin. This is the first known study to show an EMT of lung cancer cells during exposure to EC products. Because an EMT is an initial step leading to metastasis, an intractable problem that often leads to patient death, this critical finding has significant implications for former or heavy cigarette smokers who are using EC and may be at risk for lung cancer or who may already have a lung tumor.
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发表时间: 2009
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