4.7 Article

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

Journal

FASEB JOURNAL
Volume 22, Issue 9, Pages 3120-3128

Publisher

FEDERATION AMER SOC EXP BIOL
DOI: 10.1096/fj.08-109611

Keywords

xenograft; in vivo imaging; vascular mimicry; cell fusion; tumor microenvironment; glioma

Funding

  1. Norwegian Cancer Society
  2. Norwegian Research Council
  3. Innovest AS
  4. Western Norway Regional Health Authority
  5. Haukeland University Hospital, Bergen, Norway
  6. Bergen Translational Research Programme
  7. Centre de Recherche Public de la Sante (CRP-Sante)
  8. European Commission 6th Framework Program [504743]

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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.

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