ED-B fibronectin expression is a marker of epithelial-mesenchymal transition in translational oncology

Oncotarget. 2017 Jan 17;8(3):4914-4921. doi: 10.18632/oncotarget.13615.

Abstract

Fibronectin is a component of the extracellular matrix that links collagen fibers to integrins on the cell's surface. The splicing isoforms, containing the ED-B domain, are not expressed in adult tissues but only in tumor stroma or during embryonic development. Fibroblasts and endothelial cells express ED-B fibronectin during angiogenesis. Also cancer cells can synthetize ED-B fibronectin, but its function in tumor growth needs to be further elucidated.We evaluated the expression of ED-B fibronectin in prostate cancer cell lines: PC3 and DU145. Using TGF-β, we induced epithelial to mesenchymal transition in culture and observed an increase of ED-B fibronectin expression. Thereafter, we evaluated the expression of ED-B fibronectin in multipotent mesangiogenic progenitor cells, and in mesenchymal stromal cells. The expression of ED-B fibronectin was much higher in mesenchymal than prostate cancer cells even after the epithelial to mesenchymal transition.Epithelial to mesenchymal transition is a key step for tumor progression contributing to the metastatic spread. Therefore, circulating cancer cells could seed into the metastatic niche taking advantage from the ED-B fibronectin that secrete their own.

Keywords: ED-B; TGF-β; endothelial-to-mesenchymal transition; fibronectin; prostate cancer.

MeSH terms

  • Biomarkers, Tumor / metabolism*
  • Cell Line, Tumor
  • Cytokines / metabolism*
  • Disease Progression
  • Epithelial-Mesenchymal Transition* / drug effects
  • Fibronectins
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Mesenchymal Stem Cells / metabolism
  • Neoplasm Metastasis
  • Prostatic Neoplasms / metabolism*
  • Transforming Growth Factor beta / pharmacology
  • Up-Regulation*

Substances

  • Biomarkers, Tumor
  • Cytokines
  • FN1 protein, human
  • Fibronectins
  • Transforming Growth Factor beta