NGF-Enhanced Vasculogenic Properties of Epithelial Ovarian Cancer Cells Is Reduced by Inhibition of the COX-2/PGE(2) Signaling Axis
Epithelial ovarian cancer (EOC) is a lethal gynecological neoplasia characterized by extensive angiogenesis and overexpression of nerve growth factor (NGF). Here, we investigated the mechanism by which NGF increases vascular endothelial growth factor (VEGF) expression and the vasculogenic potential of EOC cells, as well as the contribution of the cyclooxygenase 2/prostaglandin E-2 (COX-2/PGE(2)) signaling axis to these events. EOC biopsies and ovarian cell lines were used to determine COX-2 and PGE(2) levels, as well as those of the potentially pro-angiogenic proteins c-MYC (a member of the Myc transcription factors family), survivin, and beta-catenin. We observed that COX-2 and survivin protein levels increased during EOC progression. In the EOC cell lines, NGF increased the COX-2 and PGE(2) levels. In addition, NGF increased survivin, c-MYC, and VEGF protein levels, as well as the transcriptional activity of c-MYC and beta-catenin/T-cell factor/lymphoid enhancer-binding factor (TCF-Lef) in a Tropomyosin receptor kinase A (TRKA)-dependent manner. Also, COX-2 inhibition prevented the NGF-induced increases in these proteins and reduced the angiogenic score of endothelial cells stimulated with conditioned media from EOC cells. In summary, we show here that the pro-angiogenic effect of NGF in EOC depends on the COX-2/PGE2 signaling axis. Thus, inhibition COX-2/PGE2 signaling will likely be beneficial in the treatment of EOC.
|Título según WOS:
|NGF-Enhanced Vasculogenic Properties of Epithelial Ovarian Cancer Cells Is Reduced by Inhibition of the COX-2/PGE(2) Signaling Axis
|Título según SCOPUS:
|NGF-enhanced vasculogenic properties of epithelial ovarian cancer cells is reduced by inhibition of the cox-2/pge2 signaling axis
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