CXCL12 overexpression and secretion by aging fibroblasts enhance human prostate epithelial proliferation in vitro

Lesa Begley, Christine Monteleon, Rajal B. Shah, James W. MacDonald, Jill A. Macoska

Research output: Contribution to journalArticle

83 Scopus citations

Abstract

The direct relationship between the aging process and the incidence and prevalence of both benign prostatic hyperplasia (BPH) and prostate cancer (PCa) implies that certain risk factors associated with the development of both diseases increase with the aging process. In particular, both diseases share an overly proliferative phenotype, suggesting that mechanisms that normally act to suppress cellular proliferation are disrupted or rendered dysfunctional as a consequence of the aging process. We propose that one such mechanism involves changes in the prostate microenvironment, which 'evolves' during the aging process and disrupts paracrine interactions between epithelial and associated stromal fibroblasts. We show that stromal fibroblasts isolated from the prostates of men 63-81 years of age at the time of surgery express and secrete higher levels of the CXCL12 chemokine compared with those isolated from younger men, and stimulate CXCR4-mediated signaling pathways that induce cellular proliferation. These studies represent an important first step towards a mechanistic elucidation of the role of aging in the etiology of benign and malignant prostatic diseases.

Original languageEnglish (US)
Pages (from-to)291-298
Number of pages8
JournalAging Cell
Volume4
Issue number6
DOIs
StatePublished - Dec 1 2005
Externally publishedYes

Keywords

  • Aging
  • CXCL12
  • Paracrine
  • Proliferation
  • Prostate

ASJC Scopus subject areas

  • Aging
  • Cell Biology

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