Quantitative changes in the protein and miRNA cargo of plasma exosome-like vesicles after exposure to ionizing radiation

Yentrapalli, Ramesh; Merl-Pham, Juliane; Azimzadeh, Omid; Mutschelknaus, Lisa; Peters, Carsten; Hauck, Stefanie M.; Atkinson, Michael J.; Tapio, Soile; Moertl, Simone

doi:10.1080/09553002.2017.1294772

Cited by 67 publications

(50 citation statements)

References 74 publications

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“…Previous reports have demonstrated that exosomes from irradiated cells can trigger apoptosis in unirradiated cells, an effect known as the bystander effect [39,40], and that hypoxic exosomes can upregulate angiogenesis [41,42]. However, our study further shows that exosome uptake by hypoxic cancer cells can be modulated by exposing the cells producing the exosomes to hypoxia and/or ionizing radiation.…”

Section: Discussionmentioning

confidence: 41%

Development and MPI tracking of novel hypoxia-targeted theranostic exosomes

et al. 2018

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Treating the hypoxic region of the tumor remains a significant challenge. The goals of this study are to develop an exosome platform that can target regions of tumor hypoxia and that can be monitored in vivo using magnetic particle imaging (MPI). Four types of exosomes (generated under hypoxic or normoxic conditions, and with or without exposure to X-ray radiation) were isolated from MDA-MB-231 human breast cancer cells. Exosomes were labeled by DiO, a fluorescent lipophilic tracer, to quantify their uptake by hypoxic cancer cells. Subsequently, the exosomes were modified to carry SPIO (superparamagnetic iron oxide) nanoparticles and Olaparib (PARP inhibitor). FACS and fluorescence microscopy showed that hypoxic cells preferentially take up exosomes released by hypoxic cells, compared with other exosome formulations. In addition, the distribution of SPIO-labeled exosomes was successively imaged in vivo using MPI. Finally, the therapeutic efficacy of Olaparib-loaded exosomes was demonstrated by increased apoptosis and slower tumor growth in vivo. Our novel theranostic platform could be used as an effective strategy to monitor exosomes in vivo and deliver therapeutics to hypoxic tumors.

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Section: Discussionmentioning

confidence: 41%

Development and MPI tracking of novel hypoxia-targeted theranostic exosomes

et al. 2018

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“…It is revealed that some miRs with elevated expression during VC promote osteogenesis via targeting at anti‐calcification proteins or contractile markers, whereas some other miRs with decreased expression suppress osteogenesis of VSMCs through targeting at osteogenic transcription factors (shown in Table ). As described, some of such miRs, including miR‐133b, miR‐204, miR‐211, alter during VC and are also proven to be transported by exosomes to modulate the biological behaviour in various kinds of recipient cells . Such results indicated that exosomes could participate in VC through transporting miRs to influence phenotype transition.…”

Section: Exosomes Participate In Vcmentioning

confidence: 73%

Exosomes, the message transporters in vascular calcification

Zhang

Huang

et al. 2018

J Cellular Molecular Medi

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Vascular calcification (VC) is caused by hydroxyapatite deposition in the intimal and medial layers of the vascular wall, leading to severe cardiovascular events in patients with hypertension, chronic kidney disease and diabetes mellitus. VC occurrences involve complicated mechanism networks, such as matrix vesicles or exosomes production, osteogenic differentiation, reduced cell viability, aging and so on. However, with present therapeutic methods targeting at VC ineffectively, novel targets for VC treatment are demanded. Exosomes are proven to participate in VC and function as initializers for mineral deposition. Secreted exosomes loaded with microRNAs are also demonstrated to modulate VC procession in recipient vascular smooth muscle cells. In this review, we targeted at the roles of exosomes during VC, especially at their effects on transporting biological information among cells. Moreover, we will discuss the potential mechanisms of exosomes in VC.

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“…A major mechanism of radioresistance in cancer cells is altered expression of DDR components and DNA repair pathway such as NHEJ or homologous recombination (HR). Numerous studies have shown that miRNA expression changes in response to DNA damage in order to regulate DDR and DNA repair pathways [29,33,67]. To identify the impact of miRNAs on DNA repair and radioresistance, Hatano et al transfected 810 different miRNA mimics separately into LNCaP-MLuc cells and then irradiated the miR-transfected cells with 4 Gy dose [55].…”

Section: Mirnas In Response To Radiotherapymentioning

confidence: 99%

microRNAs identified in prostate cancer: Correlative studies on response to ionizing radiation

et al. 2020

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As the most frequently diagnosed non-skin cancer in men and a leading cause of cancer-related death, understanding the molecular mechanisms that drive treatment resistance in prostate cancer poses a significant clinical need. Radiotherapy is one of the most widely used treatments for prostate cancer, along with surgery, hormone therapy, and chemotherapy. However, inherent radioresistance of tumor cells can reduce local control and ultimately lead to poor patient outcomes, such as recurrence, metastasis and death. The underlying mechanisms of radioresistance have not been fully elucidated, but it has been suggested that miRNAs play a critical role. miRNAs are small non-coding RNAs that regulate gene expression in every signaling pathway of the cell, with one miRNA often having multiple targets. By fine-tuning gene expression, miRNAs are important players in modulating DNA damage response, cell death, tumor aggression and the tumor microenvironment, and can ultimately affect a tumor's response to radiotherapy. Furthermore, much interest has focused on miRNAs found in biofluids and their potential utility in various clinical applications. In this review, we summarize the current knowledge on miRNA deregulation after irradiation and the associated functional outcomes, with a focus on prostate cancer. In addition, we discuss the utility of circulating miRNAs as non-invasive biomarkers to diagnose, predict response to treatment, and prognosticate patient outcomes.

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Quantitative changes in the protein and miRNA cargo of plasma exosome-like vesicles after exposure to ionizing radiation

Abstract: This study provides evidence that radiation-induced changes occur in the protein and miRNA cargo of plasma ELVs. These data imply a novel systemic communication pathway between irradiated and non-irradiated cells and tissues.

Cited by 67 publications

References 74 publications

Development and MPI tracking of novel hypoxia-targeted theranostic exosomes

Development and MPI tracking of novel hypoxia-targeted theranostic exosomes

Exosomes, the message transporters in vascular calcification

microRNAs identified in prostate cancer: Correlative studies on response to ionizing radiation

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