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A novel eGFP-expressing immunodeficient mouse model to study tumor-host interactions

Simone P. Niclou^*,1, Claude Danzeisen^*, Hans P. Eikesdal, Helge Wiig, Nicolaas H. C. Brons, Aurélie M. F. Poli, Agnete Svendsen, Anja Torsvik, Per Øyvind Enger, Jorge A. Terzis^* and Rolf Bjerkvig^*,

^* NorLux Neuro-Oncology Laboratory,

Core Facility Flowcytometry, and

Laboratoire d’Immunogénétique et d’Allergologie (LIGA), Centre de Recherche Public de la Santé (CRP-Santé), Luxembourg; and

Department of Biomedicine, University of Bergen, Bergen, Norway

¹Correspondence: CRP-Santé, NorLux Neuro-Oncology Laboratory, 84, Val Fleuri, L-1526 Luxembourg. E-mail: simone.niclou{at}crp-sante.lu

A NOD/Scid mouse expressing enhanced green fluorescent protein (eGFP) is described, in which human and mouse tumors marked with red fluorescent protein can be established in vivo, both at subcutaneous and orthotopic locations. Using light microscopy as well as multiphoton confocal microscopy techniques, we visualized in detail the intricate colocalization of tumor and host cells in situ. Moreover, using fluorescence-activated cell sorting (FACS), we were able to completely separate the host cells from the tumor cells, thus providing a system for detailed cellular and molecular analysis of tumor-host cell interactions. The fact that tumor and host cells can be reliably identified also allowed us to detect double-positive cells, possibly arising from cell fusion events or horizontal gene transfer. Similarly, the model can be applied for the detection of circulating metastatic cells and for detailed studies on the vascular compartments within tumors, including vasculogenic mimicry. Thus, the model described should provide significant insight into how tumor cells communicate with their microenvironment.—Niclou, S. P., Danzeisen, C., Eikesdal, H. P., Wiig, H., Brons, N. H. C., Poli, A. M. F., Svendsen, A., Torsvik, A., Enger, P. Ø., Terzis, J. A., Bjerkvig, R. A novel eGFP-expressing immunodeficient mouse model to study tumor-host interactions.

Key Words: xenograft • in vivo imaging • vascular mimicry • cell fusion • tumor microenvironment • glioma