Inhibition of FGF Receptor Activity in Glioma Implanted Into the Mouse Brain Using the Tetracyclin-Regulated Expression System

Angiogenesis. 2004;7(2):105-13. doi: 10.1007/s10456-004-1037-0.

Abstract

We have investigated growth and vascularization of malignant glioma in mice upon conditional inhibition of fibroblast growth factor (FGF) receptor activity. C6 rat glioma cells were transfected with a dominant-negative fibroblast growth factor receptor-2 (FGFR2-DN) cDNA under the control of a tetracycline-regulated expression promoter (tet off) and implanted in the brain of immunodeficient mice. Magnetic resonance imaging analysis showed a significant decrease in tumor growth 14 days after implantation when FGFR2-DN was expressed compared to control. This size difference disappeared after 20 days. However, after 20 days, tumor and endothelial cells apoptosis were higher in the FGFR2-DN group and consequently angiogenesis was decreased whereas tumor cells were similarly associated with blood vessels at the tumor periphery. Pericyte coverage was not different between the two groups but a higher amount of pericytes not associated with vessels was found in the FGFR2-DN expressing group. This demonstrates, that conditional expression of inhibitor of FGF receptor activity in gliomas implanted in the brain of immunodeficient mice can be achieved efficiently, and that FGFs are major players in glioma development and in glioma angiogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Brain / metabolism*
  • Cell Line, Tumor
  • Cell Proliferation
  • Gene Expression Regulation / drug effects
  • Genetic Vectors
  • Glioma / blood supply
  • Glioma / etiology*
  • Glioma / pathology
  • Mice
  • Neoplasm Transplantation
  • Neovascularization, Pathologic / etiology
  • Rats
  • Receptor Protein-Tyrosine Kinases / antagonists & inhibitors
  • Receptor Protein-Tyrosine Kinases / genetics
  • Receptor Protein-Tyrosine Kinases / physiology*
  • Receptor, Fibroblast Growth Factor, Type 2
  • Receptors, Fibroblast Growth Factor / antagonists & inhibitors
  • Receptors, Fibroblast Growth Factor / genetics
  • Receptors, Fibroblast Growth Factor / physiology*
  • Tetracycline / pharmacology
  • Transfection / methods*
  • Vascular Endothelial Growth Factor A / analysis

Substances

  • Receptors, Fibroblast Growth Factor
  • Vascular Endothelial Growth Factor A
  • Fgfr2 protein, mouse
  • Fgfr2 protein, rat
  • Receptor Protein-Tyrosine Kinases
  • Receptor, Fibroblast Growth Factor, Type 2
  • Tetracycline