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

Cancer Biology & Therapy
|December 14, 2007
PubMed

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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