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A transgenic Tie2-GFP athymic mouse model; a tool for vascular biology in xenograft tumors
Authors:Hillen Femke  Kaijzel Eric L  Castermans Karolien  oude Egbrink Mirjam G A  Löwik Clemens W G M  Griffioen Arjan W
Institution:a Department of Pathology, Angiogenesis Laboratory, Research Institute for Growth and Development (GROW), University Hospital Maastricht, P.O. Box 5800, 6202 AZ Maastricht, The Netherlands
b Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center, Leiden, The Netherlands
c Department of Physiology, Laboratory for Microcirculation, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands
Abstract:We report the generation of a transgenic Tie2-GFP athymic nude mouse, carrying green fluorescent blood vessels throughout the body. This transgenic mouse is a tool for studies in vascular biology, and is especially of interest for imaging of tumor angiogenesis and the study of anti-angiogenesis strategies in (human) xenografts. Intravital microscopy identified the presence of blood conducting structures that are not lined by endothelial cells. Dedifferentiation of aggressive tumor cells can lead to acquisition of endothelial characteristics. This process of tumor cell plasticity, also referred to as vasculogenic mimicry, has been suggested to contribute to the circulatory system in a tumor. In plastic EW7 Ewing sarcoma tumors in these Tie2-GFP mice, we observed blood flow in both regular blood vessels and non-fluorescent tumor cell-lined channels, visualizing in vivo hemodynamics in vasculogenic channels. These results demonstrate that the transgenic Tie2-GFP athymic mouse model is a valuable tool for vascular biology research.
Keywords:Intravital microscopy  Hemodynamics  In vivo  GFP vessels  Vasculogenic mimicry
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