Nicotine induces cell proliferation, invasion and epithelial-mesenchymal transition in a variety of human cancer cell lines

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^*

来源：International Journal of Cancer, 2009, 124(1): 36-45.

DOI：10.1002/ijc.23894

• lung cancer
• nicotine
• epithelial-mesenchymal transition
• tumor progression
• metastasis

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 this study, we demonstrate that nicotine can promote anchorage-independent growth in NSCLCs. In addition, nicotine also induces morphological changes characteristic of a migratory, invasive phenotype in NSCLCs on collagen gel. These morphological changes were similar to those induced by the promigratory growth factor VEGF. The proinvasive effects of nicotine were mediated by alpha 7-nAChRs on NSCLCs. RT-PCR analysis showed that the alpha 7-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 proinvasive 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 (EMT), 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.

• 出版日期2009-1-1