Regulation of soluble VEGFR-2 secreted by microvascular endothelial cells derived from human BPH

Prostate Cancer Prostatic Dis. 2012 Jun;15(2):157-64. doi: 10.1038/pcan.2011.63. Epub 2011 Dec 20.

Abstract

Background: Recently, it was reported that the soluble vascular endothelial growth factor receptor-2 (sVEGFR-2) is secreted by microvascular endothelial cells from human BPH (HPECs). The purpose of this study was to investigate the modulation of sVEGFR-2 by common endothelial cell stimulators. In addition, the physiological role of sVEGFR-2 with regard to the VEGF-stimulated proliferation of HPEC was investigated.

Methods: HPECs were isolated and cultured from fresh BPH tissue. After the incubation of HPECs either with adenosine triphosphate (ATP), interleukin (IL)-6, IL-8 or IL-12, the secretion of sVEGFR-2 was measured by enzyme-linked immunosorbent assay. For measurement of HPEC proliferation influenced by sVEGFR-2, VEGF-stimulated HPEC was cultured with/without sVEGFR-2. Cell proliferation was assessed with the Alamar Blue method.

Results: The sVEGFR-2 secretion was increased by ATP and decreased by IL-12 and IL-8, respectively. IL-6 did not show any significant effect on sVEGFR-2 secretion of HPECs. HPEC proliferation was significantly inhibited by sVEGFR-2.

Conclusions: In this study, our data suggest that the secretion of sVEGFR-2 by microvascular endothelial cells from prostate origin is influenced by multiple endothelial cell stimulators. Furthermore, our data suggest that sVEGFR-2 acts as an antiangiogenic factor.

MeSH terms

  • Adenosine Triphosphate / pharmacology
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / metabolism
  • Humans
  • Interleukin-12 / pharmacology
  • Interleukin-6 / pharmacology
  • Interleukin-8 / pharmacology
  • Male
  • Prostate / metabolism
  • Prostatic Hyperplasia / metabolism
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism*

Substances

  • Interleukin-6
  • Interleukin-8
  • Interleukin-12
  • Adenosine Triphosphate
  • Vascular Endothelial Growth Factor Receptor-2