PDGF BB induces VEGF secretion in ovarian cancer.

Academic Article

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.
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    Keywords

  • Antineoplastic Agents, Ascitic Fluid, Becaplermin, Benzamides, Cell Line, Tumor, Cystadenoma, Papillary, Female, Humans, Imatinib Mesylate, Neoplasm Proteins, Ovarian Neoplasms, Ovary, Peritoneal Neoplasms, Phosphatidylinositol 3-Kinases, Piperazines, Platelet-Derived Growth Factor, Protein Kinase Inhibitors, Proto-Oncogene Proteins c-akt, Proto-Oncogene Proteins c-sis, Pyrimidines, Receptor, Platelet-Derived Growth Factor alpha, Receptor, Platelet-Derived Growth Factor beta, Recombinant Fusion Proteins, Signal Transduction, Vascular Endothelial Growth Factor A
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    Author List

  • Matei D; Kelich S; Cao L; Menning N; Emerson RE; Rao J; Jeng MH; Sledge GW
  • Start Page

  • 1951
  • End Page

  • 1959
  • Volume

  • 6
  • Issue

  • 12