In vitro inhibition of angiogenesis by antibodies directed against the 37kDa/67kDa laminin receptor

PLoS One. 2013;8(3):e58888. doi: 10.1371/journal.pone.0058888. Epub 2013 Mar 12.

Abstract

The 37kDa/67kDa laminin receptor (LRP/LR) is a central receptor mediating interactions between tumour cells and the basement membrane and is thereby a key player in adhesion and invasion, essential processes in metastatic cancer. To affect continued tumour growth, tumours induce angiogenesis for the constant delivery of nutrients and oxygen. This study aims to determine the blocking effect of the anti-LRP/LR specific antibody, W3 on the angiogenic potential of HUVE (human umbilical vein endothelial) cells. Flow cytometric analysis revealed that 97% of HUVE cells display cell surface LRP/LR. An angiogenesis assay was conducted employing HUVE cells seeded on the basement membrane reconstituent Matrigel™ supplemented with the pro-angiogenic factor vascular endothelial growth factor (VEGF). Post 18h incubation at 37°C tubular structures, namely tube lengths were assessed. Treatment of established tubular structures with 100 µg/ml anti-LRP/LR specific antibody completely blocked angiogenesis. Our findings suggest a central role of the 37kDa/67kDa LRP/LR in tube formation and recommends anti-LRP/LR specific antibodies as potential therapeutic tools for treatment of tumour angiogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / pharmacology*
  • Antibodies, Monoclonal / pharmacology*
  • Cell Membrane / metabolism
  • Cells, Cultured
  • Human Umbilical Vein Endothelial Cells / drug effects
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Humans
  • Neovascularization, Physiologic / drug effects*
  • Platelet Endothelial Cell Adhesion Molecule-1 / metabolism
  • Receptors, Laminin / antagonists & inhibitors*
  • Vascular Endothelial Growth Factor A / pharmacology

Substances

  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal
  • Platelet Endothelial Cell Adhesion Molecule-1
  • Receptors, Laminin
  • Vascular Endothelial Growth Factor A

Grants and funding

This work was supported by the National Research Foundation, the Republic of South Africa and the Medical Research Council, the Republic of South Africa. Any opinions, findings and conclusions or recommendations expressed in this material are those of the author(s), and therefore, the National Research Foundation does not accept any liability in this regard thereto. The funders had no role in study design, data collection and analysis, decision to publish,or preparation of the manuscript.