An immune-inflammation gene expression signature in prostate tumors of smokers

Prueitt, R. L.
Wallace, T. A.
Glynn, S. A.
Yi, M.
Tang, W.
Luo, J.
Dorsey, T. H.
Stagliano, K. E.
Gillespie, J. W.
Hudson, R. S.
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Prueitt, R. L. Wallace, T. A.; Glynn, S. A.; Yi, M.; Tang, W.; Luo, J.; Dorsey, T. H.; Stagliano, K. E.; Gillespie, J. W.; Hudson, R. S.; Terunuma, A.; Shoe, J. L.; Haines, D. C.; Yfantis, H. G.; Han, M.; Martin, D. N.; Jordan, S. V.; Borin, J. F.; Naslund, M. J.; Alexander, R. B.; Stephens, R. M.; Loffredo, C. A.; Lee, D. H.; Putluri, N.; Sreekumar, A.; Hurwitz, A. A.; Ambs, S. (2015). An immune-inflammation gene expression signature in prostate tumors of smokers. Cancer Research 76 (5), 1055-1065
Smokers develop metastatic prostate cancer more frequently than nonsmokers, suggesting that a tobacco-derived factor is driving metastatic progression. To identify smoking-induced alterations in human prostate cancer, we analyzed gene and protein expression patterns in tumors collected from current, past, and never smokers. By this route, we elucidated a distinct pattern of molecular alterations characterized by an immune and inflammation signature in tumors from current smokers that were either attenuated or absent in past and never smokers. Specifically, this signature included elevated immunoglobulin expression by tumor-infiltrating B cells, NF-kappa B activation, and increased chemo-kine expression. In an alternate approach to characterize smoking induced oncogenic alterations, we also explored the effects of nicotine in human prostate cancer cells and prostate cancer-prone TRAMP mice. These investigations showed that nicotine increased glutamine consumption and invasiveness of cancer cells in vitro and accelerated metastatic progression in tumor-bearing TRAMP mice. Overall, our findings suggest that nicotine is sufficient to induce a phenotype resembling the epidemiology of smoking-associated prostate cancer progression, illuminating a novel candidate driver underlying metastatic prostate cancer in current smokers. (C)2016 AACR.
American Association for Cancer Research (AACR)
Publisher DOI
Attribution-NonCommercial-NoDerivs 3.0 Ireland