The role of extracellular-5'-nucleotidase/CD73 in glioma peritumoural brain edema

Neurol Sci. 2016 Apr;37(4):603-11. doi: 10.1007/s10072-016-2510-4. Epub 2016 Feb 16.

Abstract

During pathological conditions, extracellular-5'-nucleotidase/CD73 can protect neurons by reducing the permeability of the blood brain barrier. In recent years, it has been demonstrated that CD73 can negatively contribute to the growth of gliomas; however, the function of CD73 in glioma blood vessels is not clear. We analysed the expression of CD73 in 72 glioma patients using immunohistochemistry and correspondingly compared the results with the Edema index (EI). We established an in vitro model of the blood-tumour barrier and analysed the expression of CD73 in vascular endothelial cells. Lastly, CD73 expression was inhibited in endothelial cells, and the effects of this inhibition on tight junction structure and transendothelial resistance were observed. Compared to normal brains, the expression of CD73 in blood vessels of glioma patients was significantly decreased, and the amount was lower in the centre of the tumour than the periphery. The proportion of CD73-positive blood vessels had a positive correlation with the EI. The expression of CD73 in the in vitro endothelial cell blood-tumour barrier model was decreased. Lastly, inhibiting CD73 was found to decrease the expression of tight junction related proteins in endothelial cells and to decrease the value of transendothelial electric resistance. The expression of CD73 in glioma blood vessels was significantly decreased, which may play a multi-functional role in decreasing the expression of tight junction related proteins of brain microvascular endothelial cells and may also increase blood-tumour barrier permeability and accelerate the formation of PTBE.

Keywords: Blood-tumour barrier; Extracellular-5′-nucleotidase/CD73; Peritumoural brain edema; Tight junction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5'-Nucleotidase / antagonists & inhibitors
  • 5'-Nucleotidase / metabolism*
  • Adult
  • Aged
  • Blotting, Western
  • Brain / blood supply
  • Brain / metabolism*
  • Brain / pathology
  • Brain Edema / metabolism*
  • Brain Edema / pathology
  • Brain Neoplasms / blood supply
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / pathology
  • Cell Line
  • Coculture Techniques
  • Electric Impedance
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism
  • Endothelial Cells / pathology
  • Enzyme Inhibitors / pharmacology
  • Female
  • GPI-Linked Proteins / antagonists & inhibitors
  • GPI-Linked Proteins / metabolism
  • Glioma / blood supply
  • Glioma / metabolism*
  • Glioma / pathology
  • Humans
  • Male
  • Middle Aged
  • Severity of Illness Index
  • Tight Junctions / drug effects
  • Tight Junctions / metabolism
  • Tight Junctions / pathology
  • Young Adult

Substances

  • Enzyme Inhibitors
  • GPI-Linked Proteins
  • 5'-Nucleotidase
  • NT5E protein, human