Age-related alterations in T-lymphocytes modulate key pathways in prostate tumorigenesis

Alejandra De Angulo, Robert Faris, David Cavazos, Christopher Jolly, Benajmin Daniel, Linda Degraffenried

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Background The primary risk for prostate cancer is aging, often associated with inflammation. Evidence implicates progressive age-related immune dysfunction with increased prostate cancer incidence and mortality. The aged T-cell response is characterized by increased production of pro-inflammatory cytokines, which could significantly contribute to prostate tumorigenesis through induction of key inflammation-mediated pro-survival factors. METHODS T-cell function of the young (<6 month-old) glycerol-3-phosphate acyltransferase-1 (GPAT-1) knock-out mouse mimics many of the hallmarks observed in an aged (>22-month-old) mouse. Serum and splenic T-lymphocytes from young GPAT-1-/- (6 months) and aged wild type (22 months) mice were collected for in vitro studies, including a cytokine immunoarray for serum cytokine levels, luciferase assays for NF-κB activation and Western blot analyses for protein expression. RESULTS The T-cell cytokine profile of the GPAT-1-/- mice mirrored that observed in aged wild type mice, including higher expression levels of IL-17. Serum- and T-cell-derived factors induced NF-κB activity in normal, non-transformed and prostate cancer epithelial cells, correlating with re-localization of NF-κB and increased protein expression of downstream targets of NF-κB. CONCLUSION The aging and aging-mimic mice produced circulating factors that induce pro-inflammatory pathways in prostate cells, most notably NF-κB. These findings provide evidence that an aged T-cell may directly contribute to the increased risk for prostate cancer in the elderly and establish that the GPAT-1-/- model, which mimics many of the characteristics of an aged immune system, is a viable tool for investigating this novel area of cancer risk. Prostate 73: 855-864, 2013. © 2013 Wiley Periodicals, Inc.

Original languageEnglish (US)
Pages (from-to)855-864
Number of pages10
JournalProstate
Volume73
Issue number8
DOIs
StatePublished - Jun 2013

Keywords

  • NF-κB
  • aging
  • immune system
  • inflammation

ASJC Scopus subject areas

  • Oncology
  • Urology

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