Nicotine induces cell proliferation, invasion and epithelial-mesenchymal transition in a variety of human cancer cell lines.
Nicotine induces cell proliferation, invasion and epithelial-mesenchymal transition in a variety of human cancer cell lines.
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DOI：
10.1002/ijc.23894
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发表时间：
2009-01-01
影响因子：
6.4
通讯作者：
Chellappan, Srikumar
中科院分区：
文献类型：
--
作者：
Dasgupta, Piyali;Rizwani, Wasia;Pillai, Smitha;Kinkade, Rebecca;Kovacs, Michelle;Rastogi, Shipra;Banerjee, Sarmistha;Carless, Melanie;Kim, Esther;Coppola, Domenico;Haura, Eric;Chellappan, Srikumar
吸烟与非小细胞肺癌（NSCLC）的发病密切相关。尼古丁是香烟的一种活性成分，已被发现可诱导肺癌细胞系增殖。此外，尼古丁可诱导血管生成并赋予细胞抗凋亡能力。所有这些过程都是通过肺癌细胞上的烟碱型乙酰胆碱受体（nAChRs）介导的。在本研究中，我们证明尼古丁可促进非小细胞肺癌的非贴壁依赖性生长。此外，在胶原蛋白凝胶上，尼古丁还诱导非小细胞肺癌出现具有迁移、侵袭表型特征的形态学变化。这些形态学变化与促迁移生长因子血管内皮生长因子（VEGF）诱导的变化相似。尼古丁的促侵袭作用是由非小细胞肺癌上的α7 - nAChRs介导的。逆转录聚合酶链反应（RT - PCR）分析表明，α7 - nAChRs在人乳腺癌和胰腺癌细胞系中也有表达。研究发现尼古丁可促进人乳腺癌细胞的增殖和侵袭。在乳腺癌细胞中，尼古丁的促侵袭作用是通过一种烟碱型乙酰胆碱受体、Src和钙依赖的信号通路介导的。同样，尼古丁也可诱导Aspc1胰腺癌细胞的增殖和侵袭。最重要的是，尼古丁可诱导基因表达发生变化，符合上皮 - 间质转化特征，表现为上皮标记物如E - 钙黏蛋白表达降低、紧密连接蛋白ZO - 1染色减少，同时人乳腺癌和肺癌细胞中间质蛋白如波形蛋白和纤连蛋白水平升高。因此，尼古丁诱导侵袭和上皮 - 间质转化的能力可能有助于乳腺癌和肺癌的进展。
Cigarette smoking is strongly correlated with the onset of non-small cell lung cancer (NSCLC). Nicotine, an active component of cigarettes, has been found to induce proliferation of lung cancer cell lines. In addition, nicotine can induce angiogenesis and confer resistance to apoptosis. All these events are mediated through the nicotinic acetylcholine receptors (nAChRs) on lung cancer cells. In the present study we demonstrate that nicotine can promote anchorage-independent growth in NSCLCs. In addition, nicotine also induced morphological changes characteristic of a migratory, invasive phenotype in NSCLCs on collagen gel. These morphological changes were similar to those induced by the pro-migratory growth factor VEGF. The pro-invasive effects of nicotine were mediated by α7-nAChRs on NSCLCs. RT-PCR analysis showed that the α7-nAChRs were also expressed on human breast cancer and pancreatic cancer cell lines. Nicotine was found to promote proliferation and invasion in human breast cancer. The pro-invasive effects of nicotine were mediated via a nAChR, Src and calcium dependent signaling pathway in breast cancer cells. In a similar fashion nicotine could also induce proliferation and invasion of Aspc1 pancreatic cancer cells. Most importantly, nicotine could induce changes in gene expression consistent with epithelial to mesenchymal transition, characterized by reduction of epithelial markers like E-cadherin expression, ZO-1 staining and concomitant increase in levels of mesenchymal proteins like vimentin and fibronectin in human breast and lung cancer cells. Therefore, it is probable that the ability of nicotine to induce invasion and EMT may contribute to the progression of breast and lung cancers.
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影响因子：
6.1
作者：
Kanda, Yasunari;Watanabe, Yasuhiro
通讯作者：
Watanabe, Yasuhiro
影响因子：
15.9
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3.5
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