Tracking of Tumor Cell-Derived Extracellular Vesicles In Vivo Reveals a Specific Distribution Pattern with Consecutive Biological Effects on Target Sites of Metastasis.
Extracellular vesicles
Metastasis
Optical imaging
Proteomics
Journal
Molecular imaging and biology
ISSN: 1860-2002
Titre abrégé: Mol Imaging Biol
Pays: United States
ID NLM: 101125610
Informations de publication
Date de publication:
12 2020
12 2020
Historique:
received:
12
05
2020
accepted:
21
07
2020
revised:
16
07
2020
pubmed:
2
8
2020
medline:
6
8
2021
entrez:
2
8
2020
Statut:
ppublish
Résumé
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. 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. 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. 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.
Identifiants
pubmed: 32737655
doi: 10.1007/s11307-020-01521-9
pii: 10.1007/s11307-020-01521-9
pmc: PMC7666295
doi:
Substances chimiques
Proteome
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1501-1510Références
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