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 E2 (COX-2/
PGE2) signaling axis to these events. EOC biopsies and ovarian cell lines were used to determine COX-2 and
PGE2 levels, as well as those of the potentially pro-
angiogenic proteins c-MYC (a member of the Myc
transcription factors family),
survivin, and β-
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
PGE2 levels. In addition,
NGF increased
survivin, c-MYC, and
VEGF protein levels, as well as the transcriptional activity of c-MYC and β-
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.