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Updated: Jul 9, 2026

Evaluating the Angiogenetic Properties of Ovarian Cancer Stem-Like Cells using the Three-Dimensional Co-Culture System, NICO-1
Published on: December 5, 2020
PDGF BB induces VEGF secretion in ovarian cancer
Daniela Matei1, Stephanie Kelich, Liyun Cao
1Department of Medicine, Indiana University Melvin and Bren Simon Cancer Center and Walther Oncology Center, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA. dmatei@iupui.edu
Abstract:
We identified the platelet derived growth factor receptor (PDGFR) as a potential target in epithelial ovarian carcinoma (EOC). This led us to test whether inhibition of the PDGFR affects ovarian cancer cell proliferation and survival and regulates other processes critical to tumor growth and metastasis. We postulated that there is a correlation between the PDGF-PDGFR axis and the secretion of VEGF in EOC. VEGF secretion in ovarian tumors, cancer cells, serum and ascites fluid was measured by IHC, Western Blot and ELISA. We found increased VEGF expression and secretion in most ovarian tumors (by IHC), in EOC malignant ascites and in the conditioned media of primary ovarian cancer cells (quantified by ELISA). In malignant ascites, the levels of secreted PDGF BB and VEGF were strongly correlated (Pearson coefficient of correlation R = 0.728), suggesting that the two pathways interconnect. In PDGFR expressing immortalized ovarian cancer cells, PDGF potently induced VEGF secretion, while imatinib mesylate (Gleevec), a partially selective PDGFR inhibitor, reduced PDGF stimulated VEGF production to basal state. In ovarian cancer cells overexpressing constitutively active Akt, imatinib inhibited partially VEGF secretion, suggesting that the PI3K/Akt pathway is implicated in PDGF-stimulated VEGF secretion. In summary, these results suggest a correlation between the PDGF and VEGF networks in ovarian cancer cells and tumors. The effects of imatinib on VEGF secretion in tumor cells may affect the tumor microenvironment in a manner detrimental to tumor progression.
Insights
Platelet-derived growth factor receptor (PDGFR) inhibition impacts epithelial ovarian carcinoma (EOC) cell growth. Targeting PDGFR may reduce vascular endothelial growth factor (VEGF) secretion, potentially hindering tumor progression.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Epithelial ovarian carcinoma (EOC) is a significant cause of cancer mortality.
- The platelet-derived growth factor (PDGF) and its receptor (PDGFR) axis is implicated in various cancers.
- Vascular endothelial growth factor (VEGF) plays a critical role in tumor angiogenesis and metastasis.
Purpose of the Study:
- To investigate the role of the PDGF-PDGFR axis in EOC.
- To determine if PDGFR inhibition affects EOC cell proliferation, survival, and VEGF secretion.
- To explore the correlation between PDGF, PDGFR, and VEGF in EOC.
Main Methods:
- Immunohistochemistry (IHC) for VEGF expression in ovarian tumors.
- Western Blot and ELISA to quantify VEGF and PDGF BB levels in ascites, conditioned media, and serum.
- Treatment of PDGFR-expressing EOC cells with PDGF and imatinib mesylate (a PDGFR inhibitor).
- Investigation of the PI3K/Akt pathway's involvement using cells overexpressing active Akt.
Main Results:
- Elevated VEGF expression and secretion were observed in most ovarian tumors, malignant ascites, and primary EOC cell conditioned media.
- A strong positive correlation (R = 0.728) was found between PDGF BB and VEGF levels in malignant ascites.
- PDGF stimulation increased VEGF secretion in EOC cells, an effect reversed by imatinib treatment.
- Imatinib partially inhibited VEGF secretion in cells with activated Akt, indicating PI3K/Akt pathway involvement.
Conclusions:
- A significant correlation exists between PDGF and VEGF signaling networks in EOC.
- Inhibition of PDGFR by imatinib reduces VEGF secretion, potentially impacting the tumor microenvironment.
- Targeting the PDGF-PDGFR axis represents a potential therapeutic strategy for EOC by modulating VEGF production and tumor progression.
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