Combined Anti-PLGF and Anti-Endostatin Treatments Inhibit Ocular Hemangiomas

Cell Physiol Biochem. 2015;36(3):930-6. doi: 10.1159/000430267. Epub 2015 Jun 12.

Abstract

Background/aims: The degree of neovascularization determines the aggressiveness of ocular hemangiomas (OH). So far, the anti-angiogenic treatments using either antagonists against vascular endothelial growth factor A (VEGF-A), or endostatin, do not always lead to satisfactory therapeutic outcome.

Methods: We examined the VEGF receptor 1 (VEGFR1) levels in the OH specimen. We compared the effects of anti-PLGF, endostatin, as well as their combined treatments on the growth of OH in a mouse model, using bioluminescence imaging in living animals. We also examined vascularization by CD31 expression.

Results: We detected higher VEGFR1 levels in the OH, compared to paired normal tissue. Thus, we hypothesize that as a major ligand for VEGFR1, placental growth factor (PLGF) may also play a role in the neovascularization and tumorigenesis of OH. In an implanted OH model in mice, we found that both anti-PLGF and endostatin significantly decreased OH growth as well as vascularization, while combined treatments had a significantly more pronounced effect.

Conclusion: Our data suggest that combined anti-PLGF and endostatin may be a more effective therapy for inhibition of ocular vascularization and the tumor growth in OH.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / pharmacology*
  • Animals
  • Antibodies, Monoclonal / pharmacology*
  • Drug Synergism
  • Endostatins / pharmacology*
  • Eye Neoplasms / drug therapy*
  • Eye Neoplasms / genetics
  • Eye Neoplasms / metabolism
  • Eye Neoplasms / pathology
  • Gene Expression Regulation, Neoplastic
  • Genes, Reporter
  • Hemangioma / drug therapy*
  • Hemangioma / genetics
  • Hemangioma / metabolism
  • Hemangioma / pathology
  • Humans
  • Luciferases / genetics
  • Luciferases / metabolism
  • Male
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Neovascularization, Pathologic / drug therapy*
  • Neovascularization, Pathologic / genetics
  • Neovascularization, Pathologic / metabolism
  • Neovascularization, Pathologic / pathology
  • Placenta Growth Factor
  • Platelet Endothelial Cell Adhesion Molecule-1 / genetics
  • Platelet Endothelial Cell Adhesion Molecule-1 / metabolism
  • Pregnancy Proteins / antagonists & inhibitors*
  • Pregnancy Proteins / genetics
  • Pregnancy Proteins / metabolism
  • Vascular Endothelial Growth Factor Receptor-1 / antagonists & inhibitors
  • Vascular Endothelial Growth Factor Receptor-1 / genetics
  • Vascular Endothelial Growth Factor Receptor-1 / metabolism
  • Xenograft Model Antitumor Assays

Substances

  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal
  • Endostatins
  • PGF protein, human
  • Pgf protein, mouse
  • Platelet Endothelial Cell Adhesion Molecule-1
  • Pregnancy Proteins
  • Placenta Growth Factor
  • Luciferases
  • Vascular Endothelial Growth Factor Receptor-1