Tracking of Tumor Cell–Derived Extracellular Vesicles In Vivo Reveals a Specific Distribution Pattern with Consecutive Biological Effects on Target Sites of Metastasis
| Autor: | Simone König, Cornelius Faber, Michel Eisenblätter, Lilo Greune, Mirjam Gerwing, Anne Helfen, Johannes Roth, Moritz Wildgruber, Max Masthoff, Miriam Stölting, Walter Heindel, Katarzyna Barczyk-Kahlert, Vanessa Kocman, M. Alexander Schmidt |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Proteomics Cancer Research Proteome T cell Cell Optical imaging Flow cytometry Metastasis 03 medical and health sciences 0302 clinical medicine Cell Line Tumor Neoplasms Extracellular medicine Animals Radiology Nuclear Medicine and imaging Tissue Distribution Neoplasm Metastasis Mice Inbred BALB C medicine.diagnostic_test Chemistry Vesicle Extracellular vesicles Cell biology Kinetics 030104 developmental biology medicine.anatomical_structure Oncology 030220 oncology & carcinogenesis Female Ex vivo CD8 Intracellular Research Article |
| Zdroj: | Molecular Imaging and Biology |
| ISSN: | 1860-2002 1536-1632 |
| Popis: | Purpose Extracellular vesicles, small vesicles carrying inter alia proteins, miRNA and RNA, are important mediators of intercellular communication. The purpose of this study was to assess the distribution of extracellular vesicles from highly malignant breast cancer and their subsequent effect on the immune cell infiltrate in target organs of metastasis. Procedures Extracellular vesicles were isolated from the tissue culture supernatant of highly malignant 4T1 breast cancer cells or the serum of healthy BALB/c mice. The purity of the isolate was verified by electron microscopy and western blotting. Extracellular vesicles were additionally subjected to proteome analysis. After labeling with the fluorescent dye DiR, extracellular vesicles were injected into healthy BALB/c mice and their in vivo distribution was assessed using fluorescence reflectance imaging (FRI). Following ex vivo imaging of the organs, lung tissue samples were analyzed for extracellular vesicle-mediated changes of myeloid cells and T cell numbers, using flow cytometry. Proteome analysis revealed major differences in the cargo of tumor cell–derived versus extracellular vesicles from healthy serum. Results In contrast to control extracellular vesicles, DiR-labeled extracellular vesicles from tumor cells preferentially accumulated in lung, liver, and spine. Subsequent flow cytometry of the immune cell composition of lung tissue samples revealed an increase of cytotoxic CD8+ T cells and a decrease of CD4+ T-helper cells as well as an increase in mature macrophages in response to tumor cell EV. Conclusions In conclusion, distribution of tumor cell–derived extracellular vesicles follows a specific pattern and can be monitored, using dedicated imaging. Extracellular vesicles alter the immune cell composition in target organs of metastasis, using a specific proteome cargo. |
| Databáze: | OpenAIRE |
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