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

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.

Keywords: cigarette smoke extract; early carcinogenesis; leukoplakia; oral squamous cell carcinoma; smoking.