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

Hikita, Tomoya; Miyata, Mamiko; Watanabe, Risayo; Oneyama, Chitose

doi:10.1038/s41598-020-73580-5

Cited by 26 publications

(28 citation statements)

References 42 publications

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“…Moreover, AkaBLI with video-rate was able to monitor signals from the brain striatum in freely moving mice and common marmoset. Although AkaBLI was sufficiently utilized for deep-tissue imaging, this system was not enabled to quantitatively detect signals from exosomes [ 54 ]. This result suggests the need for new luciferin analogues that produce sufficient light, even under low-ATP-concentration conditions.…”

Section: Chemical and Physical Characteristics Of The Nir Luciferimentioning

confidence: 99%

“…Since the FMZ/NanoLuc ® reaction is independent of the concentration of ATP [ 52 ], it is a useful tool for studying exosomes, blood, and urine, where ATP abundance is limited [ 53 ]. This is particularly important because the native firefly bioluminescence reaction is not suitable for monitoring exosomes [ 54 ], as it is ATP-dependent. However, generally, CTZ and derivatives are proceeded by auto-oxidation, in the absence of luciferase, resulting high background signals are detected in cell or animal experiments [ 55 ].…”

Section: Introductionmentioning

confidence: 99%

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How to Select Firefly Luciferin Analogues for In Vivo Imaging

Saito-Moriya

Nakayama²,

Kamiya

et al. 2021

IJMS

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Bioluminescence reactions are widely applied in optical in vivo imaging in the life science and medical fields. Such reactions produce light upon the oxidation of a luciferin (substrate) catalyzed by a luciferase (enzyme), and this bioluminescence enables the quantification of tumor cells and gene expression in animal models. Many researchers have developed single-color or multicolor bioluminescence systems based on artificial luciferin analogues and/or luciferase mutants, for application in vivo bioluminescence imaging (BLI). In the current review, we focus on the characteristics of firefly BLI technology and discuss the development of luciferin analogues for high-resolution in vivo BLI. In addition, we discuss the novel luciferin analogues TokeOni and seMpai, which show potential as high-sensitivity in vivo BLI reagents.

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Section: Chemical and Physical Characteristics Of The Nir Luciferimentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

How to Select Firefly Luciferin Analogues for In Vivo Imaging

Saito-Moriya

Nakayama²,

Kamiya

et al. 2021

IJMS

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“…Asteltoxin decreased the luminescence level observed in the culture medium for PC3 cells expressing CD63-Antares2 (PC3/CD63-Antares2) (Fig. 1 C) 30 . CD63-positive EVs from PC3 cells were 100–150 nm in size and their particle number was decreased by asteltoxin in a dose-dependent manner (Supplementally Fig.…”

Section: Resultsmentioning

confidence: 84%

Asteltoxin inhibits extracellular vesicle production through AMPK/mTOR-mediated activation of lysosome function

Mitani

Lin

Sakamoto

et al. 2022

Sci Rep

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Cancer cells secrete aberrantly large amounts of extracellular vesicles (EVs) including exosomes, which originate from multivesicular bodies (MVBs). Because EVs potentially contribute to tumor progression, EV inhibitors are of interest as novel therapeutics. We screened a fungal natural product library. Using cancer cells engineered to secrete luciferase-labeled EVs, we identified asteltoxin, which inhibits mitochondrial ATP synthase, as an EV inhibitor. Low concentrations of asteltoxin inhibited EV secretion without inducing mitochondrial damage. Asteltoxin attenuated cellular ATP levels and induced AMPK-mediated mTORC1 inactivation. Consequently, MiT/TFE transcription factors are translocated into the nucleus, promoting transcription of lysosomal genes and lysosome activation. Electron microscopy analysis revealed that the number of lysosomes increased relative to that of MVBs and the level of EVs decreased after treatment with asteltoxin or rapamycin, an mTORC1 inhibitor. These findings suggest that asteltoxin represents a new type of EV inhibitor that controls MVB fate.

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“…Multiple studies have employed orthotopic and heterotopic tumor models to study the biodistribution of exosomes [83,84] as well as to dissect the role of exosomes in tumorigenesis [43], metastasis [85], and immunosuppression [86]. These models are sometimes used in conjunction with intravenous/systemic delivery of exosomes, isolated either from cultured cell lines or from patient samples, to study their short-term and long-term accumulation as well as effects on the tumor microenvironment.…”

Section: In Vivo Models For the Study Of Tumor-associated Exosomesmentioning

confidence: 99%

Tumor-Associated Exosomes: A Potential Therapeutic Target for Restoring Anti-Tumor T Cell Responses in Human Tumor Microenvironments

Shenoy

Bhatta

Bankert

2021

Cells

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Exosomes are a subset of extracellular vesicles (EVs) that are released by cells and play a variety of physiological roles including regulation of the immune system. Exosomes are heterogeneous and present in vast numbers in tumor microenvironments. A large subset of these vesicles has been demonstrated to be immunosuppressive. In this review, we focus on the suppression of T cell function by exosomes in human tumor microenvironments. We start with a brief introduction to exosomes, with emphasis on their biogenesis, isolation and characterization. Next, we discuss the immunosuppressive effect of exosomes on T cells, reviewing in vitro studies demonstrating the role of different proteins, nucleic acids and lipids known to be associated with exosome-mediated suppression of T cell function. Here, we also discuss initial proof-of-principle studies that established the potential for rescuing T cell function by blocking or targeting exosomes. In the final section, we review different in vivo models that were utilized to study as well as target exosome-mediated immunosuppression, highlighting the Xenomimetic mouse (X-mouse) model and the Omental Tumor Xenograft (OTX) model that were featured in a recent study to evaluate the efficacy of a novel phosphatidylserine-binding molecule for targeting immunosuppressive tumor-associated exosomes.

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

Cited by 26 publications

References 42 publications

How to Select Firefly Luciferin Analogues for In Vivo Imaging

How to Select Firefly Luciferin Analogues for In Vivo Imaging

Asteltoxin inhibits extracellular vesicle production through AMPK/mTOR-mediated activation of lysosome function

Tumor-Associated Exosomes: A Potential Therapeutic Target for Restoring Anti-Tumor T Cell Responses in Human Tumor Microenvironments

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