Title |
An Immune-Inflammation Gene Expression Signature in Prostate Tumors of Smokers
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Published in |
Cancer Research, February 2016
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DOI | 10.1158/0008-5472.can-14-3630 |
Pubmed ID | |
Authors |
Robyn L Prueitt, Tiffany A Wallace, Sharon A Glynn, Ming Yi, Wei Tang, Jun Luo, Tiffany H Dorsey, Katherine E Stagliano, John W Gillespie, Robert S Hudson, Atsushi Terunuma, Jennifer L Shoe, Diana C Haines, Harris G Yfantis, Misop Han, Damali N Martin, Symone V Jordan, James F Borin, Michael J Naslund, Richard B Alexander, Robert M Stephens, Christopher A Loffredo, Dong H Lee, Nagireddy Putluri, Arun Sreekumar, Arthur A Hurwitz, Stefan Ambs |
Abstract |
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-κB activation, and increased chemokine 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 suggested that nicotine was 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. |
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Geographical breakdown
Country | Count | As % |
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United States | 1 | 17% |
Russia | 1 | 17% |
Unknown | 4 | 67% |
Demographic breakdown
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Members of the public | 5 | 83% |
Science communicators (journalists, bloggers, editors) | 1 | 17% |
Mendeley readers
Geographical breakdown
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Germany | 2 | 4% |
United Kingdom | 1 | 2% |
Unknown | 49 | 94% |
Demographic breakdown
Readers by professional status | Count | As % |
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Researcher | 14 | 27% |
Student > Bachelor | 7 | 13% |
Student > Ph. D. Student | 6 | 12% |
Professor | 5 | 10% |
Student > Master | 4 | 8% |
Other | 11 | 21% |
Unknown | 5 | 10% |
Readers by discipline | Count | As % |
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Biochemistry, Genetics and Molecular Biology | 12 | 23% |
Medicine and Dentistry | 12 | 23% |
Agricultural and Biological Sciences | 6 | 12% |
Computer Science | 3 | 6% |
Nursing and Health Professions | 2 | 4% |
Other | 7 | 13% |
Unknown | 10 | 19% |