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An Immune-Inflammation Gene Expression Signature in Prostate Tumors of Smokers
- Source :
- Cancer research. 76(5)
- Publication Year :
- 2014
-
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.
- Subjects :
- 0301 basic medicine
PCA3
Male
Cancer Research
Nicotine
Immunoglobulins
Inflammation
Biology
Article
nicotinic acetylcholine-receptors
03 medical and health sciences
Prostate cancer
Mice
0302 clinical medicine
Prostate
Cell Line, Tumor
nf-kappa-b
medicine
Animals
Humans
mouse models
Neoplasm Invasiveness
Neoplasm Metastasis
Lung cancer
Cell Nucleus
cigarette-smoking
Interleukin-8
Smoking
NF-kappa B
Cancer
Prostatic Neoplasms
squamous-cell carcinoma
medicine.disease
030104 developmental biology
medicine.anatomical_structure
Oncology
030220 oncology & carcinogenesis
Immunology
Cancer cell
Cancer research
lung-cancer
signaling promotes
medicine.symptom
Transcriptome
Proto-Oncogene Proteins c-akt
cancer tissue
Tramp
endothelial growth-factor
Subjects
Details
- ISSN :
- 15387445
- Volume :
- 76
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- Cancer research
- Accession number :
- edsair.doi.dedup.....3a4d877eb37930747df8746c321c3a73