VEGF/VEGFR2 Autocrine Signaling Stimulates Metastasis in Prostate Cancer Cells

Vascular endothelial growth factor receptor 2 (VEGFR2) is a tyrosine kinase receptor for the angiogenic growth factor, VEGF. VEGFR2 is typically found in hematopoietic stem cells and endothelial cells. We report the expression of VEGFR2 on highly metastatic human prostate cancer cells. Using real-time RTPCR, immunoprecipitation, western blotting, ELISA, and radioligand crosslinking, we demonstrate the expression and activation of VEGFR2 in malignant prostate tumor cells. Functionally, VEGF induced the proliferation of PC3MLN4 cells and VEGFR2 kinase inhibitors attenuated their growth. PC3MLN4 orthotopic prostate tumors in immunodeficient mice were larger, more vascular, and showed increased metastasis to lymph nodes compared to parental PC3M tumors. PC3M cells transfected with VEGFR2 show increased migration toward VEGF. Taken together, our data suggest that VEGF may act as an autocrine growth factor in aggressive prostate cancer cells. Therapies targeting VEGFR2 may directly and indirectly (by affecting angiogenesis) inhibit prostate cancer progression.