An Immune and Inflammation Signature in Prostate Tumors of Smokers (part 3)

Current smokers develop metastatic prostate cancer more frequently than nonsmokers, suggesting that a tobacco-derived factor induces metastasis. To identify smoking-induced alterations in human prostate tumors, we analyzed gene and protein expression of tumors from current, past, and never smokers and observed distinct molecular alterations in current smokers. Specifically, an immune and inflammation signature was identified in prostate tumors of current smokers that was either attenuated or absent in past and never smokers. Key characteristics of this signature included augmented immunoglobulin expression by tumor-infiltrating B cells, NF-kB activation, and increased interleukin-8 in tumor and blood. In an alternate approach to characterize smoking-induced oncogenic alterations, we explored the effects of nicotine in prostate cancer cells and prostate cancer-prone TRAMP mice. These experiments showed that nicotine increases both invasiveness of human prostate cancer cells and metastasis in tumor-bearing TRAMP mice, indicating that nicotine can induce a phenotype that resembles the epidemiology of smoking-associated prostate cancer progression. In summary, we describe distinct oncogenic alterations in prostate tumors from current smokers and show that nicotine can enhance prostate cancer metastasis.

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Prueitt RL, Wallace TA, Glynn SA, Yi M, Tang W, Luo J, Dorsey TH, Stagliano KE, Gillespie JW, Hudson RS, Terunuma A, Shoe JL, Haines DC, Yfantis HG, Han M, Martin DN, Jordan SV, Borin JF, Naslund MJ, Alexander RB, Stephens RM, Loffredo CA, Lee DH, Putluri N, Sreekumar A, Hurwitz AA, Ambs S