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  • In vivo imaging of long-term accumulation of cancer-derived exosomes using a BRET-based reporter.

In vivo imaging of long-term accumulation of cancer-derived exosomes using a BRET-based reporter.

Scientific reports (2020-10-08)
Tomoya Hikita, Mamiko Miyata, Risayo Watanabe, Chitose Oneyama
ZUSAMMENFASSUNG

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.

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GW4869, ≥90% (NMR)