期刊
GYNECOLOGIC ONCOLOGY
卷 115, 期 3, 页码 414-423出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ygyno.2009.08.019
关键词
VEGF(121); VEGF(165); VEGFR-2; Small interference RNA (siRNA); Epithelial ovarian cancer (EOC); LPA
资金
- Kaleidoscope of Life Foundation
- Greenberg Foundation
- SAC Foundation
- 100 Woman in Hedge Fund
- NYU Cancer Institute
- Varadi Ovarian Initiative for Cancer Education
- Sailfish Foundation
- NYU School of Medicine
- NYU Cancer Institute and Mount Sinai School of Medicine
Background. The VEGF-VEGF receptor (VEGFR) signaling axis has emerged as a promising target for cancer therapy, attributing to its vital role in tumor angiogenesis and growth. We have previously reported the regulation of epithelial ovarian cancer (EOC) invasion and migration by VEGF and the implication of VEGF-VEGFR-2 axis in lysophosphaticlic acid (LPA)-induced EOC invasion. However, the expression profile of VEGF and VEGFRs in EOC, their association with tumor aggressiveness, and their regulation by LPA remain unclear. Objectives and methods. In this Study, we examined the expression of VEGFR-1, VEGFR-2, neuropilin-1 (NRP-1), NRP-2, VEGF(121), and VEGF(165) in established EOC cell lines and assessed their correlation with cell invasiveness. Moreover, using an ovarian cancer tissue qPCR array, we analyzed VEGFR-2 expression across a panel of 48 tissues with different disease stages and histological grades. We also tested the effect of LPA on VEGF and VEGFR-2 expression and examined whether blocking VEGFR-2 by RNA interference (RNAi) affects LPA-induced EOC invasion. Results. We show that VEGF and VEGFR-2 expression Correlates with cell invasiveness and VEGFR-2 expression in ovarian cancer tissues correlate with tumor grade. In addition, LPA, at 20 mu m, significantly induced the expression of VEGF(121), VEGF(165), and VEGFR-2 in SKOV3 and DOV13 cells (P<0.05). VEGFR-2 small interference RNA (siRNA) transfection remarkably decreased LPA's invasion-promoting effect (P<0.001) in SKOV3 cells without significantly decreasing SKOV3 cells' basal invasiveness. In DOV13 cells,VEGFR-2 silencing significantly decreases both the basal level cell invasion and LPA's invasion promoting effect (P<0.001). Conclusion. These results suggest that decreasing VEGFR-2 expression by RNAi may prove to be an effective method to reduce the metastatic potential of EOC cells exposed to elevated levels of LPA. (C) 2009 Elsevier Inc. All rights reserved.
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