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Title: Enhancement of cancer stem-like and epithelial−mesenchymal transdifferentiation property in oral epithelial cells with long-term nicotine exposure: Reversal by targeting SNAIL

Abstract

Cigarette smoking is one of the major risk factors in the development and further progression of tumorigenesis, including oral squamous cell carcinoma (OSCC). Recent studies suggest that interplay cancer stem-like cells (CSCs) and epithelial−mesenchymal transdifferentiation (EMT) properties are responsible for the tumor maintenance and metastasis in OSCC. The aim of the present study was to investigate the effects of long-term exposure with nicotine, a major component in cigarette, on CSCs and EMT characteristics. The possible reversal regulators were further explored in nicotine-induced CSCs and EMT properties in human oral epithelial (OE) cells. Long-term exposure with nicotine was demonstrated to up-regulate ALDH1 population in normal gingival and primary OSCC OE cells dose-dependently. Moreover, long-term nicotine treatment was found to enhance the self-renewal sphere-forming ability and stemness gene signatures expression and EMT regulators in OE cells. The migration/cell invasiveness/anchorage independent growth and in vivo tumor growth by nude mice xenotransplantation assay was enhanced in long-term nicotine-stimulated OE cells. Knockdown of Snail in long-term nicotine-treated OE cells was found to reduce their CSCs properties. Therapeutic delivery of Si-Snail significantly blocked the xenograft tumorigenesis of long-term nicotine-treated OSCC cells and largely significantly improved the recipient survival. The present study demonstrated that the enrichment ofmore » CSCs coupled EMT property in oral epithelial cells induced by nicotine is critical for the development of OSCC tumorigenesis. Targeting Snail might offer a new strategy for the treatment of OSCC patients with smoking habit. -- Highlights: ► Sustained nicotine treatment induced CSCs properties of oral epithelial cells. ► Long-term nicotine treatment enhance EMT properties of oral epithelial cells. ► Long-term nicotine exposure increased tumorigenicity of oral epithelial cells. ► Si-Snail blocked xenograft tumorigenesis of long-term nicotine-treated OSCC cells.« less

Authors:
 [1];  [2]
  1. Institute of Oral Science, Chung Shan Medical University, Taichung, Taiwan (China)
  2. School of Dentistry, Chung Shan Medical University, Taichung, Taiwan (China)
Publication Date:
OSTI Identifier:
22216060
Resource Type:
Journal Article
Journal Name:
Toxicology and Applied Pharmacology
Additional Journal Information:
Journal Volume: 266; Journal Issue: 3; Other Information: Copyright (c) 2012 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0041-008X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; CARCINOMAS; DOSES; ENRICHMENT; GENES; HEALTH HAZARDS; IN VIVO; METASTASES; MICE; NICOTINE; SNAILS; TOBACCO PRODUCTS; TOBACCO SMOKES

Citation Formats

Yu, Cheng-Chia, School of Dentistry, Chung Shan Medical University, Taichung, Taiwan, Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan, Chang, Yu-Chao, and Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan. Enhancement of cancer stem-like and epithelial−mesenchymal transdifferentiation property in oral epithelial cells with long-term nicotine exposure: Reversal by targeting SNAIL. United States: N. p., 2013. Web. doi:10.1016/J.TAAP.2012.11.023.
Yu, Cheng-Chia, School of Dentistry, Chung Shan Medical University, Taichung, Taiwan, Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan, Chang, Yu-Chao, & Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan. Enhancement of cancer stem-like and epithelial−mesenchymal transdifferentiation property in oral epithelial cells with long-term nicotine exposure: Reversal by targeting SNAIL. United States. https://doi.org/10.1016/J.TAAP.2012.11.023
Yu, Cheng-Chia, School of Dentistry, Chung Shan Medical University, Taichung, Taiwan, Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan, Chang, Yu-Chao, and Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan. 2013. "Enhancement of cancer stem-like and epithelial−mesenchymal transdifferentiation property in oral epithelial cells with long-term nicotine exposure: Reversal by targeting SNAIL". United States. https://doi.org/10.1016/J.TAAP.2012.11.023.
@article{osti_22216060,
title = {Enhancement of cancer stem-like and epithelial−mesenchymal transdifferentiation property in oral epithelial cells with long-term nicotine exposure: Reversal by targeting SNAIL},
author = {Yu, Cheng-Chia and School of Dentistry, Chung Shan Medical University, Taichung, Taiwan and Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan and Chang, Yu-Chao and Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan},
abstractNote = {Cigarette smoking is one of the major risk factors in the development and further progression of tumorigenesis, including oral squamous cell carcinoma (OSCC). Recent studies suggest that interplay cancer stem-like cells (CSCs) and epithelial−mesenchymal transdifferentiation (EMT) properties are responsible for the tumor maintenance and metastasis in OSCC. The aim of the present study was to investigate the effects of long-term exposure with nicotine, a major component in cigarette, on CSCs and EMT characteristics. The possible reversal regulators were further explored in nicotine-induced CSCs and EMT properties in human oral epithelial (OE) cells. Long-term exposure with nicotine was demonstrated to up-regulate ALDH1 population in normal gingival and primary OSCC OE cells dose-dependently. Moreover, long-term nicotine treatment was found to enhance the self-renewal sphere-forming ability and stemness gene signatures expression and EMT regulators in OE cells. The migration/cell invasiveness/anchorage independent growth and in vivo tumor growth by nude mice xenotransplantation assay was enhanced in long-term nicotine-stimulated OE cells. Knockdown of Snail in long-term nicotine-treated OE cells was found to reduce their CSCs properties. Therapeutic delivery of Si-Snail significantly blocked the xenograft tumorigenesis of long-term nicotine-treated OSCC cells and largely significantly improved the recipient survival. The present study demonstrated that the enrichment of CSCs coupled EMT property in oral epithelial cells induced by nicotine is critical for the development of OSCC tumorigenesis. Targeting Snail might offer a new strategy for the treatment of OSCC patients with smoking habit. -- Highlights: ► Sustained nicotine treatment induced CSCs properties of oral epithelial cells. ► Long-term nicotine treatment enhance EMT properties of oral epithelial cells. ► Long-term nicotine exposure increased tumorigenicity of oral epithelial cells. ► Si-Snail blocked xenograft tumorigenesis of long-term nicotine-treated OSCC cells.},
doi = {10.1016/J.TAAP.2012.11.023},
url = {https://www.osti.gov/biblio/22216060}, journal = {Toxicology and Applied Pharmacology},
issn = {0041-008X},
number = 3,
volume = 266,
place = {United States},
year = {Fri Feb 01 00:00:00 EST 2013},
month = {Fri Feb 01 00:00:00 EST 2013}
}