Project description:Tobacco exposure has been established to be a major risk factor for developing oral squamous cell carcinoma (OSCC). The purpose of this study is to identify potential biomarkers to distinguish the biological effectsof combustible tobacco products from that of non-combustible tobacco products using normal human gingival epithelial cells (HGEC), non-metastatic (101A) and metastatic (101B) OSCC cell lines.
Project description:Cigarette smoking exerts diverse physiological effects including immune suppression. Existing US epidemiological data show that consumption of smokeless tobacco products, such as moist snuff, is less harmful relative to cigarette smoking. In efforts to understand the molecular changes due to consumption of different tobacco product classes, we have shown recently that smokers exhibit distinct peripheral blood mononuclear cells (PBMCs) gene expression patterns relative to moist snuff users and non-tobacco consumers (NTCs). To better characterize the biological effects exerted from the use of different tobacco products, a genome-wide gene expression study, using a cultured PBMC model, was performed. Global gene expression profiling results showed that 5,421 genes (2,809 upregulated and 2,612 downregulated) were dose-dependently changed by WSCM (pFDR < 0.01). Some gene expression changes detected in the cultured system were also observed in clinical studies. For example, FEZ1 and SLAMF7 were suppressed by WSCM while CCR2 and HHEX genes were upregulated by WSCM commonly in the cultured experiment and clinical studies. WSCM exposures, but not STE, uniquely affected genes involved in immune cell development and inflammatory response. Ingenuity Pathway Analysis identified upstream regulators, such as TNF, IL1β, and NFκB to be likely responsible for the observed gene expression changes and that these cascading signals were generally suppressed by WSCM, but not STE. Collectively, these findings sµggested that combustible and non-combustible tobacco products produce distinct biological effects which could explain the observed chronic immune suppression in smokers.
