BMP-4 expression has prognostic significance in advanced serous ovarian carcinoma and is affected by cisplatin in OVCAR-3 cells

Tumour Biol. 2011 Oct;32(5):985-95. doi: 10.1007/s13277-011-0200-7. Epub 2011 Jun 15.

Abstract

Several angiogenesis-promoting factors have prognostic significance in ovarian cancer. The objective of this study was to evaluate whether traditional chemotherapy affects angiogenesis-related factors in ovarian carcinoma and to assess the clinical significance of these effects. To screen for angiogenesis-related factors of possible relevance, OVCAR-3 and A2780 ovarian cancer cells were treated with IC(50) doses of cisplatin (CDDP) or docetaxel, or with bevacizumab, and mRNA expression of several angiogenesis-related factors was analyzed. Thrombospondin-1 (TSP-1), bone morphogenetic protein-4 (BMP-4), endothelin-1, and placental growth factor-2 were statistically significantly induced by CDDP. At protein level, CDDP also induced hypoxia-inducible factor-1α but not vascular endothelial growth factor. In carcinoma samples taken before and after platinum-based neoadjuvant chemotherapy from 28 patients with advanced, high-grade serous ovarian carcinoma, CD105 and factors most induced by CDDP (TSP-1 and BMP-4) were analyzed by immunohistochemistry. Strong expression of BMP-4 before chemotherapy was an independent prognostic factor of longer progression-free time (p = 0.002) and overall survival (p = 0.02), but it was not associated with neovascularization (as evaluated by CD105). However, changes in BMP-4 expression in samples analyzed before and after chemotherapy (observed in 22/28 patients) were not associated with prognosis. TSP-1 expression was not associated with clinical parameters. Our results indicate that in serous ovarian carcinoma, BMP-4 has prognostic significance, which is not angiogenesis-related. We also show that CDDP induces several angiogenesis-related growth factors in vitro and future studies are warranted to clarify the clinical significance of this phenomenon.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antigens, CD / biosynthesis
  • Antineoplastic Agents / pharmacology*
  • Bone Morphogenetic Protein 4 / biosynthesis*
  • Cell Line, Tumor
  • Cisplatin / pharmacology*
  • Cystadenocarcinoma, Serous / drug therapy
  • Cystadenocarcinoma, Serous / metabolism*
  • Cystadenocarcinoma, Serous / pathology
  • Endoglin
  • Female
  • Gene Expression / drug effects*
  • Humans
  • Immunoblotting
  • Immunohistochemistry
  • Middle Aged
  • Neoplasm Staging
  • Neovascularization, Pathologic / metabolism
  • Ovarian Neoplasms / drug therapy
  • Ovarian Neoplasms / metabolism*
  • Ovarian Neoplasms / pathology
  • Prognosis
  • Receptors, Cell Surface / biosynthesis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Thrombospondin 1 / biosynthesis

Substances

  • Antigens, CD
  • Antineoplastic Agents
  • BMP4 protein, human
  • Bone Morphogenetic Protein 4
  • ENG protein, human
  • Endoglin
  • Receptors, Cell Surface
  • Thrombospondin 1
  • Cisplatin