Modified model of VX2 tumor overexpressing vascular endothelial growth factor

J Vasc Interv Radiol. 2012 Jun;23(6):809-817.e2. doi: 10.1016/j.jvir.2012.02.003. Epub 2012 Apr 11.

Abstract

Purpose: To determine whether upregulated expression of vascular endothelial growth factor (VEGF) in VX2 cells can increase vessel density (VD) and reduce tumor necrosis.

Materials and methods: The VX2 cell line was transfected with expression vectors containing cDNA for rabbit VEGF. Stable clones producing rabbit VEGF (VEGF-VX2) were selected. VEGF-VX2 cells (n = 5 rabbits) or nontransfected VX2 cells (controls; n = 5 rabbits) were implanted into leg muscle of 10 rabbits. The animals were sacrificed at day 21. Tumor volume, percentage of necrosis, VD, and VEGF concentration in tumor protein extract were quantified.

Results: Overexpression of VEGF by VX2 cells augmented tumor implantation efficiency 100% and favored cyst formation. The tumor volume was significantly larger for VEGF-VX2 transfected tumors versus controls (P = .0143). Overexpression of VEGF in VX2 cells significantly increased the VD of the tumors (P = .0138). The percentage of necrosis was reduced in VEGF-VX2 tumors versus controls (19.5% vs 38.5 %; P = .002). VEGF concentration in VEGF-VX2 tumors was significantly higher than in control tumors (P = .041) and was correlated with tumor volume (ρ = .883, P = .012).

Conclusions: The overexpression of VEGF increased tumor growth and vascularization, favored cyst formation, and reduced tumor necrosis. This new phenotype of the VX2 tumor may offer some advantages over classic models of VX2 tumor for evaluating anticancer therapies.

MeSH terms

  • Animals
  • Biomarkers, Tumor / metabolism
  • Blood Vessels / metabolism*
  • Blood Vessels / pathology
  • Cell Line, Tumor
  • Genotype
  • Immunohistochemistry
  • Muscle Neoplasms / blood supply
  • Muscle Neoplasms / genetics
  • Muscle Neoplasms / metabolism*
  • Muscle Neoplasms / pathology
  • Necrosis
  • Neoplasms, Cystic, Mucinous, and Serous / blood supply
  • Neoplasms, Cystic, Mucinous, and Serous / genetics
  • Neoplasms, Cystic, Mucinous, and Serous / metabolism*
  • Neoplasms, Cystic, Mucinous, and Serous / pathology
  • Neovascularization, Pathologic
  • Phenotype
  • Platelet Endothelial Cell Adhesion Molecule-1 / metabolism
  • Rabbits
  • Time Factors
  • Transfection
  • Tumor Burden
  • Up-Regulation
  • Vascular Endothelial Growth Factor A / biosynthesis*
  • Vascular Endothelial Growth Factor A / genetics

Substances

  • Biomarkers, Tumor
  • Platelet Endothelial Cell Adhesion Molecule-1
  • Vascular Endothelial Growth Factor A