Enhanced in vitro invasiveness of ovarian cancer cells through up-regulation of VEGF and induction of MMP-2

Vascular endothelial growth factor (VEGF) has been identified to be important in tumor angiogenesis, which is essential for the growth, invasion, and metastasis of solid tumors. The aim of this study was to determine the effect of VEGF overexpression on the invasion of human epithelial ovarian cancer cells in vitro and the possible mechanism involved. The VEGF(165) cDNA was transfected into ovarian tumor cell lines CAOV3 and COC1 to promote the expression of VEGF. The VEGF expression and matrix metalloproteinase (MMP)-2 activity were examined by RT-PCR, Western blot analysis and gelatin zymography. A modified Boyden chamber assay was used to test tumor cell invasion in vitro. All cells overexpressing VEGF displayed an enhanced in vitro invasiveness through Matrigel-coated filters with Boyden chamber invasion assay. MMP-2 mRNA and protein were significantly increased during VEGF165 cDNA transfection; MMP-2 activity was also increased. The invasion property of ovarian cancer cells was abrogated with VEGF neutralizing antibody. Our data indicated that the expression of VEGF gave impetus to the in vitro invasion of ovarian cancer cells by stimulating the production and functional activities of MMP-2, which may be a key component of VEGF in promoting ovarian cancer cell invasion. VEGF may constitute a novel therapeutic target for antiangiogenic cancer therapy.