Early effects of cigarette smoke extract on human oral keratinocytes and carcinogenesis in head and neck squamous cell carcinoma

Abstract

Background Cigarette smoking is a major risk factor for head and neck squamous cell carcinoma. Still, the effect of cigarette smoke on the molecular level is unclear. The aim of the present study was to investigate the early effects of cigarette smoke on carcinogenesis of head and neck squamous cell carcinoma. Methods Human oral keratinocytes were exposed for 1 week to standardized cigarette smoke extract, and subsequently RT‐quantitative PCR array was performed. Protein expression of dysregulated genes was determined by immunohistochemistry in tissue samples of oral squamous cell carcinoma, oral leukoplakia, and tonsil mucosa. Results RT‐PCR revealed upregulation of ITGA‐2 and MMP‐1, whereas TEK receptor tyrosine kinase was downregulated in human oral keratinocytes. ITGA‐2 and MMP‐1 were significantly overexpressed in tissue samples of oral squamous cell carcinoma in comparison to normal mucosa (P <.01 in all experiments). Conclusion Upregulation of ITGA‐2 and MMP‐1 induced by cigarette smoke contributes significantly to oral carcinogenesis.

Effect of tobacco use on cadmium accumulation in the oral keratinized mucosa

“…Cd, which is believed to be effective in the development of oral cancer, is 1 of > 3,000 chemical components in tobacco products. Cd influences the formation of oral cancer because it changes the apoptotic mechanism in the mucosa [ 7 – 10 ]. In addition, the Cd level was higher in various biological samples, such as hair, blood, and dental calculus, taken from patients with oral cancer than in those from healthy individuals [ 3 , 8 , 11 , 12 ].…”