In Vitro Inhibition of Angiogenesis by Antibodies Directed against the 37kDa/67kDa Laminin Receptor |
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| Authors: | Raksha Khusal Bianca Da Costa Dias Kiashanee Moodley Clement Penny Uwe Reusch Stefan Knackmuss Melvyn Little Stefan F T Weiss |
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| Institution: | 1. School of Molecular and Cell Biology, University of the Witwatersrand, Johannesburg, Republic of South Africa.; 2. Department of Internal Medicine, University of the Witwatersrand, Johannesburg, Republic of South Africa.; 3. Affimed Therapeutics AG, Technologiepark, Im Neuenheimer Feld 582, Heidelberg, Germany.; The Scripps Research Institute Scripps Florida, United States Of America, |
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| 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. |
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