An Immune-Inflammation Gene Expression Signature in Prostate Tumors of Smokers
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. Cancer Res; 76(5); 1055–65. ©2015 AACR.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Feb 29, 2016
- Source ID
- 10.1158/0008-5472.can-14-3630
Entities
People
- Arthur A. Hurwitz
- Arun Sreekumar
- Atsushi Terunuma
- Christopher A. Loffredo
- Damali N. Martin
- Diana C. Haines
- Dong H. Lee
- Harris G. Yfantis
- James F. Borin
- Jennifer L. Shoe
- John W. Gillespie
- Jun Luo
- Katherine E. Stagliano
- Michael J. Naslund
- Ming Yi
- Misop Han
- Nagireddy Putluri
- Richard B. Alexander
- Robert M. Stephens
- Robert S. Hudson
- Robyn L. Prueitt
- Sharon A. Glynn
- Stefan Ambs
- Symone V. Jordan
- Tiffany A. Wallace
- Tiffany H. Dorsey
- Wei Tang
Organizations
- Baylor College of Medicine
- Georgetown University Medical Center
- Johns Hopkins School of Medicine
- Leidos
- National Cancer Institute
- National Science Foundation
- United States Department of Defense
- University of Maryland
- Veterans Health Administration