Investigation of a fluorescent reporter microenvironment niche labeling strategy in experimental brain metastasis

• Published in: iScience Vol. 27; no. 7; p. 110284
• Main Authors: Massara, Matteo, Dolfi, Bastien, Wischnewski, Vladimir, Nolan, Emma, Held, Werner, Malanchi, Ilaria, Joyce, Johanna A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 19-07-2024; Elsevier
• Subjects: Cancer; Cell biology; Microenvironment; Cell biology; Microenvironment; Cancer
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2024.110284

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.
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•The sLP-mCherry strategy detected host cells communicating with BrM tumor cells•CD206+ macrophages are associated with high uptake of sLP-mCherry•mCherry is taken up by CD206+ macrophages, even without the cell-penetrating tag
Microenvironment; Cell biology; Cancer