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Dadun > Depósito Académico > CIMA (Centro de Investigación Médica Aplicada) > Área de Oncología > Microambiente tumoral > DA - CIMA - Oncología - Microambiente tumoral - Artículos de revista >

Recurrent exposure to nicotine differentiates human bronchial epithelial cells via epidermal growth factor receptor activation
Authors: Martinez-Garcia, E. (Eva)
Irigoyen, M. (Marta)
Anso, E. (Elena)
Martinez-Irujo, J.J. (Juan José)
Rouzaut, A. (Ana)
Keywords: Lung epithelial cells
Issue Date: 2008
Publisher: Elsevier
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ISSN: 1096-0333
Citation: Martinez-Garcia E, Irigoyen M, Anso E, Martinez-Irujo JJ, Rouzaut A. Recurrent exposure to nicotine differentiates human bronchial epithelial cells via epidermal growth factor receptor activation. Toxicol Appl Pharmacol 2008 May 1;228(3):334-342.
Cigarette smoking is the major preventable cause of lung cancer in developed countries. Nicotine (3-(1-methyl-2-pyrrolidinyl)-pyridine) is one of the major alkaloids present in tobacco. Besides its addictive properties, its effects have been described in panoply of cell types. In fact, recent studies have shown that nicotine behaves as a tumor promoter in transformed epithelial cells. This research focuses on the effects of acute repetitive nicotine exposure on normal human bronchial epithelial cells (NHBE cells). Here we show that treatment of NHBE cells with recurrent doses of nicotine up to 500 muM triggered cell differentiation towards a neuronal-like phenotype: cells emitted filopodia and expressed neuronal markers such as neuronal cell adhesion molecule, neurofilament-M and the transcription factors neuronal N and Pax-3. We also demonstrate that nicotine treatment induced NF-kB translocation to the nucleus, phosphorylation of the epidermal growth factor receptor (EGFR), and accumulation of heparin binding-EGF in the extracellular medium. Moreover, addition of AG1478, an inhibitor of EGFR tyrosine phosphorylation, or cetuximab, a monoclonal antibody that precludes ligand binding to the same receptor, prevented cell differentiation by nicotine. Lastly, we show that differentiated cells increased their adhesion to the extracellular matrix and their protease activity. Given that several lung pathologies are strongly related to tobacco consumption, these results may help to better understand the damaging consequences of nicotine exposure.
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Appears in Collections:DA - Ciencias - Bioquímica y Biología molecular - Artículos de Revista
DA - CIMA - Oncología - Microambiente tumoral - Artículos de revista

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