title: 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.
authors.affiliation: Laboratory of Human Carcinogenesis, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA.
authors.forename: Robyn L
authors.initials: RL
authors.lastname: Prueitt
authors.affiliation: Laboratory of Human Carcinogenesis, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA.
authors.forename: Tiffany A
authors.initials: TA
authors.lastname: Wallace
authors.affiliation: Laboratory of Human Carcinogenesis, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA.
authors.forename: Sharon A
authors.initials: SA
authors.lastname: Glynn
authors.affiliation: Advanced Biomedical Computing Center, Leidos Biomedical Research/NCI, Frederick, MD, USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Yi
authors.affiliation: Laboratory of Human Carcinogenesis, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Tang
authors.affiliation: Department of Urology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Luo
authors.affiliation: Laboratory of Human Carcinogenesis, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA.
authors.forename: Tiffany H
authors.initials: TH
authors.lastname: Dorsey
authors.affiliation: Laboratory of Molecular Immunoregulation, CCR, NCI, NIH, Frederick, MD, USA.
authors.forename: Katherine E
authors.initials: KE
authors.lastname: Stagliano
authors.affiliation: Laboratory of Pathology and Urologic Oncology Branch, CCR, NCI, NIH, Bethesda, MD, USA.
authors.forename: John W
authors.initials: JW
authors.lastname: Gillespie
authors.affiliation: Laboratory of Human Carcinogenesis, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Hudson
authors.affiliation: Laboratory of Human Carcinogenesis, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Terunuma
authors.affiliation: Laboratory Animal Sciences Program, Leidos Biomedical Research, Frederick National Laboratory, Frederick, MD, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Shoe
authors.affiliation: Pathology/Histotechnology Laboratory, Leidos Biomedical Research, Frederick National Laboratory, Frederick, MD, USA.
authors.forename: Diana C
authors.initials: DC
authors.lastname: Haines
authors.affiliation: Pathology and Laboratory Medicine, Baltimore Veterans Affairs Medical Center, Baltimore, MD, USA.
authors.forename: Harris G
authors.initials: HG
authors.lastname: Yfantis
authors.affiliation: Department of Urology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: Misop
authors.initials: M
authors.lastname: Han
authors.affiliation: Laboratory of Human Carcinogenesis, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA.
authors.forename: Damali N
authors.initials: DN
authors.lastname: Martin
authors.affiliation: Laboratory of Human Carcinogenesis, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA.
authors.forename: Symone V
authors.initials: SV
authors.lastname: Jordan
authors.affiliation: Urology and Greenebaum Cancer Center, University of Maryland, MD, USA.
authors.forename: James F
authors.initials: JF
authors.lastname: Borin
authors.affiliation: Urology and Greenebaum Cancer Center, University of Maryland, MD, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Naslund
authors.affiliation: Urology and Greenebaum Cancer Center, University of Maryland, MD, USA.
authors.forename: Richard B
authors.initials: RB
authors.lastname: Alexander
authors.affiliation: Advanced Biomedical Computing Center, Leidos Biomedical Research/NCI, Frederick, MD, USA.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Stephens
authors.affiliation: Cancer Prevention and Control Program, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, USA.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Loffredo
authors.affiliation: Pathology and Laboratory Medicine, Baltimore Veterans Affairs Medical Center, Baltimore, MD, USA.
authors.forename: Dong H
authors.initials: DH
authors.lastname: Lee
authors.affiliation: Department of Molecular and Cell Biology, Verna and Marrs McLean Department of Biochemistry, Alkek Center for Molecular Discovery, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Nagireddy
authors.initials: N
authors.lastname: Putluri
authors.affiliation: Department of Molecular and Cell Biology, Verna and Marrs McLean Department of Biochemistry, Alkek Center for Molecular Discovery, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Arun
authors.initials: A
authors.lastname: Sreekumar
authors.affiliation: Laboratory of Pathology and Urologic Oncology Branch, CCR, NCI, NIH, Bethesda, MD, USA.
authors.forename: Arthur A
authors.initials: AA
authors.lastname: Hurwitz
authors.affiliation: Laboratory of Human Carcinogenesis, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA.
authors.forename: Stefan
authors.initials: S
authors.lastname: Ambs
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics; D007249:Inflammation / Q000378:metabolism*; D016209:Interleukin-8 / Q000097:blood; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009538:Nicotine / Q000494:pharmacology; D011471:Prostatic Neoplasms / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012907:Smoking / Q000009:adverse effects*; D059467:Transcriptome
chemical_list: D007136:Immunoglobulins; D016209:Interleukin-8; D016328:NF-kappa B; D009538:Nicotine; D051057:Proto-Oncogene Proteins c-akt