Secretion of soluble VEGF receptor 2 by microvascular endothelial cells derived by human benign prostatic hyperplasia.

ABSTRACT

Vascular endothelial growth factor (VEGF) is one of the most potent mitogenic factors stimulating both prostate endothelial and prostate epithelial cells. Recently, some studies reported on the endothelial secretion of a soluble VEGF receptor 2 (sVEGFR-2) that modifies the free VEGF concentration by binding VEGF. For the first time in this study, we report on the secretion and the regulation of the secretion of sVEGFR-2 by microvascular endothelial cells derived from the tissue of human benign prostatic hyperplasia (HPEC). HPEC were isolated and cultured from fresh prostate tissue. The prostate epithelial cell line BPH-1 was cultured with the supernatant of the HPEC cell culture (fractioned by fast protein liquid chromatography) and the VEGF concentration was subsequently measured. HPEC were incubated with VEGF or tumor necrosis factor alpha (TNF-alpha). Afterwards, the concentration of sVEGFR-2 in the supernatant of unstimulated and stimulated HPEC was measured by ELISA. HPEC showed a typical endothelial morphology. Under cell culture conditions sVEGFR-2 binds VEGF The measured VEGF concentration in the supernatant of BPH-1 cells was reduced when the fractions of HPEC conditioned medium with the highest sVEGFR-2 concentration were incubated with the BPH-1 cells. The sVEGFR-2 secretion of HPEC was stimulated by VEGF and TNF-alpha. For the first time we report on the secretion of sVEGFR-2 by microvascular endothelial cells of prostate origin. The secretion of sVEGFR-2 by HPEC was stimulated by VEGF and TNF-alpha. Our data suggest that sVEGFR-2 secreted by prostate endothelial cells could modify the effect of VEGF on prostate endothelial and prostate epithelial cells.