RRC ID 62618
著者 Hikita T, Miyata M, Watanabe R, Oneyama C.
タイトル In vivo imaging of long-term accumulation of cancer-derived exosomes using a BRET-based reporter.
ジャーナル Sci Rep
Abstract Monitoring of exosome dynamics in living organisms is essential to demonstrate the real functions of cancer-derived exosomes. Currently, these have been elucidated in vitro or under non-physiological conditions in vivo in most cases. To overcome these limitations, we developed an imaging method using Antares2-mediated bioluminescence resonance energy transfer (BRET) for observing long-term accumulation of exosomes in vivo. Ectopic expression of CD63-Antares2 effectively labeled exosomes with Antares2, which emitted intense, long-wavelength luminescence suitable for in vivo monitoring. Transplantation of CD63-Antares2-expressing prostate cancer cells into mice allowed determining the amount of cancer-derived exosomes released from primary tumors into the bloodstream and visualizing the long-term homing behavior of exosomes to their target organs or tissues. Interestingly, secreted exosome was decreased upon administration of low dose of dasatinib, an approved tyrosine-kinase inhibitor. The CD63-Antares2 xenograft mouse model will be useful for elucidating the dynamics of cancer-derived exosomes in vivo and evaluating the therapeutic efficacy and mechanism of exosome production inhibitors.
巻・号 10(1)
ページ 16616
公開日 2020-10-6
DOI 10.1038/s41598-020-73580-5
PII 10.1038/s41598-020-73580-5
PMID 33024173
PMC PMC7538576
MeSH Animals Bioluminescence Resonance Energy Transfer Techniques / methods* Dasatinib / pharmacology Energy Transfer* Exosomes / metabolism* Heterografts Male Mice Molecular Imaging / methods* Neoplasm Transplantation Prostatic Neoplasms / metabolism* Prostatic Neoplasms / pathology* Protein Kinase Inhibitors / pharmacology Time Factors
IF 3.998
リソース情報
遺伝子材料 pcDNA3 Venus-Akaluc (RDB15781)
ヒト・動物細胞 DU145(RCB2143) LNCap.FGC(RCB2144) PC-3(RCB2145)