Stimulation of prostate cells by the senescence phenotype of epithelial and stromal cells: Implication for benign prostate hyperplasia

Shoulei Jiang, Chung-seog Song, Bandana Chatterjee

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Hyperproliferation of prostate transition-zone epithelial and stromal cells leads to benign prostate hyperplasia (BPH), a prevalent pathology in elderly men. Senescent cells in BPH tissue induce a senescence-associated secretory phenotype (SASP) which, by generating inflamed microenvironment and reactive stroma, promotes leukocyte infiltration, cellular hyperproliferation, and nodular prostate growth. We examined human prostate epithelial (BPH-1, PNT-1α) and stromal (HPS-19I) cells for SASP induction by ionizing radiation and assessed SASP's impacts on cell proliferation and on signal transducers that promote cellular growth, proliferation, and survival. Radiation-induced DNA damage led to cellular senescence, evident from elevated expression of senescence-associated β-galactosidase and the cell-cycle inhibitor p16/INK4a. Clinical BPH tissue showed p16 accumulation. SASP induced mRNA expression for inflammatory cytokines (IL-1α, IL-6, IL-8, TNF-α); chemokines (GM-CSF, CXCL12); metalloproteases (MMP-1, MMP-3, MMP-10); growth factor binding IGFBP-3. Media from irradiated epithelial or stromal cells enhanced BPH-1 proliferation. ERK1/2 and AKT, which enhance cell growth/survival and STAT5, which facilitates cell cycle progression and leukocyte recruitment to epithelial microenvironment, were activated by SASP components. The radiation-induced cellular senescence model can be a platform for identification of individual SASP components and pathways that drive BPH etiology/progression in vivo and targeting them may form the basis for novel BPH therapy.

Original languageEnglish (US)
Pages (from-to)353-363
Number of pages11
JournalFASEB BioAdvances
Volume1
Issue number6
DOIs
StatePublished - Jun 2019

Keywords

  • AKT
  • BPH
  • ERK1/2
  • SASP
  • STAT5
  • inflammation

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology (miscellaneous)
  • Cancer Research
  • Molecular Medicine
  • Physiology

Fingerprint

Dive into the research topics of 'Stimulation of prostate cells by the senescence phenotype of epithelial and stromal cells: Implication for benign prostate hyperplasia'. Together they form a unique fingerprint.

Cite this