Autocrine activation of PDGFRα promotes the progression of ovarian cancer

D. Matei, R. E. Emerson, Y. C. Lai, L. A. Baldridge, J. Rao, C. Yiannoutsos, D. B. Donner

Research output: Contribution to journalArticle

100 Scopus citations

Abstract

Platelet-derived growth factor receptor (PDGFR)α expression was found in ovarian cancer cells and tumors by microarray hybridization. This led us to test whether ovarian cancers also produce ligands for this receptor, as this would demonstrate that such malignancies support their own growth and spread through autocrine activation. We assayed the expression of ligands for the PDGFR in ovarian tumors, cell lines and peritoneal fluid using RT-PCR, immunohistochemistry (IHC) and ELISA. We detected strong mRNA expression for the PDGFRα ligands in most ovarian tumors. Receptor and ligand expressions (PDGFRα and PDGF AB) were also detected by IHC in, respectively, 34 and 32 of 47 ovarian tumors. The stainings for PDGFRα and PDGF AB were strongly correlated (P-value = 0.014), suggesting that an autocrine loop is functional in ovarian cancer. PDGF AA and BB were quantified in peritoneal fluid by ELISA. Both ligands are secreted at higher levels in ovarian cancer ascites specimens (n = 54) than in fluid from nonmalignant disorders (n = 8). PDGF was detected in media conditioned by ovarian cancer cells. Such conditioned media induced activation of the PDGFR, Akt and MAPK and stimulated cell proliferation. A neutralizing PDGF antibody blocked these effects. Specific PDGFR inhibition by siRNA or a neutralizing antibody to the receptor inhibited PDGF-stimulated receptor activation and cell proliferation, suggesting that receptor targeting has a role in ovarian cancer treatment.

Original languageEnglish (US)
Pages (from-to)2060-2069
Number of pages10
JournalOncogene
Volume25
Issue number14
DOIs
StatePublished - Mar 30 2006

Keywords

  • Autocrine
  • Ovarian epithelial cancer
  • Platelet-derived growth factor receptor

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Fingerprint Dive into the research topics of 'Autocrine activation of PDGFRα promotes the progression of ovarian cancer'. Together they form a unique fingerprint.

  • Cite this