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

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. AlexanderRobert M. Stephens, Christopher A. Loffredo, Dong H. Lee, Nagireddy Putluri, Arun Sreekumar, Arthur A. Hurwitz, Stefan Ambs

Research output: Contribution to journalArticlepeer-review

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 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.

Original languageEnglish (US)
Pages (from-to)1055-1065
Number of pages11
JournalCancer Research
Volume76
Issue number5
DOIs
StatePublished - Mar 1 2016

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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