Next Article in Journal
Combing the Cancer Genome for Novel Kinase Drivers and New Therapeutic Targets
Previous Article in Journal
Imaging and Tissue Biomarkers of Choline Metabolism in Diffuse Adult Glioma: 18F-Fluoromethylcholine PET/CT, Magnetic Resonance Spectroscopy, and Choline Kinase α
Open AccessArticle

NGF-Enhanced Vasculogenic Properties of Epithelial Ovarian Cancer Cells Is Reduced by Inhibition of the COX-2/PGE2 Signaling Axis

1
Laboratorio de Endocrinología y Biología de la Reproducción, Hospital Clínico Universidad de Chile, Santiago 8380456, Chile
2
Departamento de Obstetricia y Ginecología, Facultad de Medicina, Universidad de Chile, Santiago 8380453, Chile
3
Laboratorio de Microbiología Celular. Instituto de Investigación e Innovación en Salud. Facultad de Ciencias de la Salud, Universidad Central de Chile, Santiago 8320000, Chile
4
Advanced Center for Chronic Diseases (ACCDIS), Santiago 8380000, Chile
5
Laboratorio de Comunicaciones Celulares, Centro de estudios en Ejercicio, Metabolismo y Cáncer (CEMC), Facultad de Medicina, Universidad de Chile, Santiago 8380453, Chile
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Cancers 2019, 11(12), 1970; https://doi.org/10.3390/cancers11121970
Received: 28 October 2019 / Revised: 17 November 2019 / Accepted: 19 November 2019 / Published: 7 December 2019
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. View Full-Text
Keywords: NGF; epithelial ovarian cancer; COX-2/PGE2; vasculogenesis; VEGF; c-MYC; survivin; beta-catenin NGF; epithelial ovarian cancer; COX-2/PGE2; vasculogenesis; VEGF; c-MYC; survivin; beta-catenin
Show Figures

Graphical abstract

MDPI and ACS Style

Garrido, M.P.; Hurtado, I.; Valenzuela-Valderrama, M.; Salvatierra, R.; Hernández, A.; Vega, M.; Selman, A.; Quest, A.F.G.; Romero, C. NGF-Enhanced Vasculogenic Properties of Epithelial Ovarian Cancer Cells Is Reduced by Inhibition of the COX-2/PGE2 Signaling Axis. Cancers 2019, 11, 1970.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop