Year: 2016
Type: article
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.
Source: Cancer Research
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
Institutions: National Institutes of Health, National Cancer Institute, Center for Cancer Research, Leidos Biomedical Research Inc. (United States), Johns Hopkins University, Johns Hopkins Medicine, Frederick National Laboratory for Cancer Research, Baltimore VA Medical Center, Georgetown University Medical Center, Georgetown Lombardi Comprehensive Cancer Center, Baylor College of Medicine, Alkek Center for Molecular Discovery
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: METABOLOMIC PROFILING TO DISTINGUISH RACIALLY DISTINCT PROGNOSTIC MARKERS IN PROSTATE CANCER, Collaborative Research: Statistical Methodology for Network based Integrative Analysis of Omics Data, G386607036, G4522976240, G4887459736, G5888954722, METABOLOMIC PROFILING AND BIOLOGIC BASIS OF RACIAL DISPARITY IN PROSTATE CANCER, G9000055294
OpenAlex ID: W2279863755