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.
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.
Ye
Feng
F
Department of Gynecologic Oncology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou 310006, China. yefyef@sohu.com
Chen
Huai-Zeng
HZ
Xie
Xing
X
Ye
Da-Feng
DF
Lu
Wei-Guo
WG
Ding
Zhi-Ming
ZM
D021581:Active Transport, Cell Nucleus / Q000502:physiology; D018952:Antigens, CD34 / Q000096:biosynthesis; D002450:Cell Communication / Q000502:physiology; D002467:Cell Nucleus / Q000378:metabolism; D003470:Culture Media; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D008894:Milk Proteins; D009842:Oligopeptides / Q000494:pharmacology; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D050796:STAT3 Transcription Factor; D050799:STAT5 Transcription Factor; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D015534:Trans-Activators / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism / Q000494:pharmacology*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*
D018952:Antigens, CD34; D003470:Culture Media; D004268:DNA-Binding Proteins; D008894:Milk Proteins; D009842:Oligopeptides; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D050799:STAT5 Transcription Factor; D015534:Trans-Activators; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D014443:Tyrosine; D040301:Vascular Endothelial Growth Factor Receptor-2