title: In vitro inhibition of angiogenesis by antibodies directed against the 37kDa/67kDa laminin receptor.
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.
authors.affiliation: School of Molecular and Cell Biology, University of the Witwatersrand, Johannesburg, Republic of South Africa.
authors.forename: Raksha
authors.initials: R
authors.lastname: Khusal
authors.forename: Bianca
authors.initials: B
authors.lastname: Da Costa Dias
authors.forename: Kiashanee
authors.initials: K
authors.lastname: Moodley
authors.forename: Clement
authors.initials: C
authors.lastname: Penny
authors.forename: Uwe
authors.initials: U
authors.lastname: Reusch
authors.forename: Stefan
authors.initials: S
authors.lastname: Knackmuss
authors.forename: Melvyn
authors.initials: M
authors.lastname: Little
authors.forename: Stefan F T
authors.initials: SF
authors.lastname: Weiss
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D017474:Receptors, Laminin / Q000037:antagonists & inhibitors*; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology
chemical_list: D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D017474:Receptors, Laminin; D042461:Vascular Endothelial Growth Factor A
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