Investigation of a fluorescent reporter microenvironment niche labeling strategy in experimental brain metastasis
Matteo Massara,
Bastien Dolfi,
Vladimir Wischnewski,
Emma Nolan,
Werner Held,
Ilaria Malanchi,
Johanna A. Joyce
Affiliations
Matteo Massara
Department of Oncology, University of Lausanne, 1011 Lausanne, Switzerland; Ludwig Institute for Cancer Research, University of Lausanne 1011 Lausanne, Switzerland; Agora Cancer Research Centre Lausanne, 1011 Lausanne, Switzerland; L. Lundin and Family Brain Tumor Research Center, Departments of Oncology and Clinical Neurosciences, Centre Hospitalier Universitaire Vaudois, 1011 Lausanne, Switzerland
Bastien Dolfi
Department of Oncology, University of Lausanne, 1011 Lausanne, Switzerland; Ludwig Institute for Cancer Research, University of Lausanne 1011 Lausanne, Switzerland; Agora Cancer Research Centre Lausanne, 1011 Lausanne, Switzerland; L. Lundin and Family Brain Tumor Research Center, Departments of Oncology and Clinical Neurosciences, Centre Hospitalier Universitaire Vaudois, 1011 Lausanne, Switzerland
Vladimir Wischnewski
Department of Oncology, University of Lausanne, 1011 Lausanne, Switzerland; Ludwig Institute for Cancer Research, University of Lausanne 1011 Lausanne, Switzerland; Agora Cancer Research Centre Lausanne, 1011 Lausanne, Switzerland; L. Lundin and Family Brain Tumor Research Center, Departments of Oncology and Clinical Neurosciences, Centre Hospitalier Universitaire Vaudois, 1011 Lausanne, Switzerland
Emma Nolan
Tumour-Host Interaction Laboratory, The Francis Crick Institute, London NW1 1AT, UK
Werner Held
Department of Oncology, University of Lausanne, 1011 Lausanne, Switzerland
Ilaria Malanchi
Tumour-Host Interaction Laboratory, The Francis Crick Institute, London NW1 1AT, UK
Johanna A. Joyce
Department of Oncology, University of Lausanne, 1011 Lausanne, Switzerland; Ludwig Institute for Cancer Research, University of Lausanne 1011 Lausanne, Switzerland; Agora Cancer Research Centre Lausanne, 1011 Lausanne, Switzerland; L. Lundin and Family Brain Tumor Research Center, Departments of Oncology and Clinical Neurosciences, Centre Hospitalier Universitaire Vaudois, 1011 Lausanne, Switzerland; Corresponding author
Summary: Brain metastases are the most common brain tumors in patients and are associated with poor prognosis. Investigating the colonization and outgrowth of brain metastases is challenging given the complexity of the organ, tissue sampling difficulty, and limited experimental models. To address this challenge, we employed a strategy to analyze the metastatic niche in established lesions, based on the release of a cell-penetrating mCherry tag from labeled tumor cells to neighboring niche cells, using different brain metastasis mouse models. We found that CD206+ macrophages were the most abundant cells taking up the mCherry label in established metastases. In vitro and in vivo experiments demonstrated that macrophages uptake and retain the canonical form of mCherry, even without the cell-penetrating portion of the tag. These results identify a specific macrophage subset in the brain that retains tumor-supplied fluorescent molecules, thereby complicating the long-term use of niche labeling strategies in established experimental brain metastasis.
