Vascular endothelial growth factor (VEGF) and ovarian carcinoma cell supernatant activate signal transducers and activators of transcription (STATs) via VEGF receptor-2 (KDR) in human hemopoietic progenitor cells

Abstract

Objective. To investigate the STATs signaling pathway activated by VEGF in human hemopoietic progenitor cells. Methods. CD34 + hemopoietic progenitor cells, which isolated from umbilical cord blood, were treated with VEGF or culture supernatant of ovarian carcinoma cell line which could secrete large amount of VEGF, phosphorylation and nuclear translocation of STAT3 and STAT5 were then detected by Western Blot and immunocytochemistry. Expression of VEGFR2/KDR on CD34 + cells was studied by immunocytochemistry. The specific VEGFR2/KDR heptapeptide antagonist ATWLPPR was used to identify whether the activation of STATs signaling pathway was specifically mediated by VEGFR2/KDR. Results. The concentration of VEGF in SKOV3-supernatant was 4024.84± 505.59 pg/ml. CD34 + progenitor cells could express VEGFR2/KDR. When CD34 + cells were stimulated by VEGF and SKOV3-supernatant, STAT3 appeared tyrosine-phosphorylation and nuclear translocation, but STAT5 was only phosphorylated, and not translocated. When ATWLPPR was used to block the binding of VEGF to KDR, VEGF and the SKOV3-supernatant failed to activate the phosphorylation of STAT3 and STAT5. Conclusions. STAT3 may participate in the signal transduction pathways activated by VEGF specifically mediated by VEGFR2/KDR in human hemopoietic progenitor cells, and the aforementioned signaling pathway participated in the interaction of ovarian carcinoma cells and progenitor cells.