Extracellular matrix metalloproteinase inducer (EMMPRIN) expression correlates positively with active angiogenesis and negatively with basic fibroblast growth factor expression in epithelial ovarian cancer

J Cancer Res Clin Oncol. 2014 Mar;140(3):361-9. doi: 10.1007/s00432-013-1569-z. Epub 2013 Dec 28.

Abstract

Purpose: The primary aim of this paper was to evaluate the expression of extracellular matrix metalloproteinase inducer (EMMPRIN) and its relationship with proangiogenic factors and microvessel density (MVD) in ovarian cancer.

Methods: The study group included 58 epithelial ovarian cancers (EOCs), 35 benign ovarian tumors, and 21 normal ovaries. The expression of EMMPRIN, vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (bFGF) was assessed by ELISA of tissue homogenates. Antibodies against CD105, CD31, and CD34 were used to immunohistochemically assess MVD.

Results: We have found significantly higher EMMPRIN expression in EOC than in benign ovarian tumors and normal ovaries. Similarly, the VEGF expression was higher in EOC than in benign ovarian tumors and normal ovaries. By contrast, bFGF expression was lower in EOC than in benign ovarian tumors and ovary samples. EMMPRIN expression in EOC was directly correlated with VEGF expression and CD105-MVD, but inversely correlated with bFGF expression. Grade 2/3 ovarian cancers had increased expression of EMMPRIN and VEGF, increased CD105-MVD, and lowered expression of bFGF compared to grade 1 ovarian cancers. Moreover, EMMPRIN expression was higher in advanced (FIGO III and IV) ovarian cancer.

Conclusions: The upregulation of EMMPRIN and VEGF expression is correlated with increased CD105-MVD and silenced bFGF, which suggests early and/or reactivated angiogenesis in ovarian cancer. Aggressive EOC is characterized by the following: high expression of EMMPRIN and VEGF, high CD105-MVD, and low expression of bFGF.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma, Clear Cell / metabolism
  • Adenocarcinoma, Mucinous / metabolism
  • Antigens, CD / metabolism*
  • Basigin / metabolism*
  • Carcinoma / metabolism*
  • Carcinoma, Endometrioid / metabolism
  • Carcinoma, Ovarian Epithelial
  • Cystadenocarcinoma, Serous / metabolism
  • Endoglin
  • Enzyme Induction
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Fibroblast Growth Factor 2 / metabolism*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry
  • Microcirculation
  • Middle Aged
  • Neoplasms, Glandular and Epithelial / enzymology
  • Neoplasms, Glandular and Epithelial / metabolism*
  • Neovascularization, Pathologic / metabolism*
  • Ovarian Neoplasms / enzymology
  • Ovarian Neoplasms / metabolism*
  • Receptors, Cell Surface / metabolism*
  • Up-Regulation
  • Vascular Endothelial Growth Factor A / metabolism*

Substances

  • Antigens, CD
  • BSG protein, human
  • ENG protein, human
  • Endoglin
  • Receptors, Cell Surface
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Fibroblast Growth Factor 2
  • Basigin