Ultra-sensitive liquid biopsy of circulating extracellular vesicles using ExoScreen

Yoshioka, Yusuke; Kosaka, Nobuyoshi; Konishi, Yuki; Ohta, Hiroyuki; Okamoto, Hiroyuki; Sonoda, Hidenori; Nonaka, Ryoji; Yamamoto, Hirofumi; Ishii, Hideshi; Mori, Masaki; Furuta, Koh; Nakajima, Takeshi; Hayashi, Hiroshi; Sugisaki, Hajime; Higashimoto, Hiroko; Kato, Takashi; Takeshita, Fumitaka; Ochiya, Takahiro

doi:10.1038/ncomms4591

Cited by 481 publications

(429 citation statements)

References 22 publications

(28 reference statements)

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“…Rather, this strategy can be clinically applied via the use of antibodies that target specific proteins on the surfaces of cancer-derived EVs. Molecules that are specific to the surfaces of cancer-derived EVs have been surveyed as cancer biomarkers and include CD147 in colon cancer 37 and CD24 and EpCAM in ovarian cancer. 40 Recently, EVs from several cancer cells have been found to display integrin b 1 , whereas normal cells did not; thus, this is a possible therapeutic target.…”

Section: Discussionmentioning

confidence: 99%

“…The EVs were diluted into RPMI 1640 medium without FBS. After removing the spent medium, 3 mg/100 mL of EVs with antibodies or only EVs were added to the cells, which were then incubated at 37 C for 15 hr. The EVs that remained in the supernatant were quantified using a Synergy H4 plate reader (BioTek) at excitation/emission wavelengths of 480/502 nm.…”

Section: In Vitro Macrophage Uptake Assaymentioning

confidence: 99%

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Disruption of Circulating Extracellular Vesicles as a Novel Therapeutic Strategy against Cancer Metastasis

Nishida-Aoki¹,

Tominaga²,

et al. 2017

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Metastasis is the main cause of cancer mortality for many types of cancer; however, difficulties remain in effectively preventing metastasis. It has been recently and widely reported that cancer-derived extracellular vesicles (EVs) contribute to cancer metastasis. Thus, therapeutic strategies targeting cancerderived EVs hold great promise because of the possibility of EVs driving the cancer microenvironment toward metastasis. Here, we provide a novel strategy for therapeutic antibody treatment to target cancer-derived EVs and inhibit the metastasis of breast cancer in a mouse model, establishing a rationale for further clinical investigation. Treatment with human-specific anti-CD9 or anti-CD63 antibodies significantly decreased metastasis to the lungs, lymph nodes, and thoracic cavity, although no obvious effects on primary xenograft tumor growths were observed. In in vitro and in vivo experiments, the EVs incubated with the targeted antibodies were preferentially internalized by macrophages, suggesting that antibody-tagged cancer-derived EVs would be eliminated by macrophages. Our results suggested that therapeutic antibody administration effectively suppresses EV-triggered metastasis in cancer and that the removal of EVs could be a novel strategy for cancer therapy.

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Section: Discussionmentioning

confidence: 99%

Section: In Vitro Macrophage Uptake Assaymentioning

confidence: 99%

Disruption of Circulating Extracellular Vesicles as a Novel Therapeutic Strategy against Cancer Metastasis

Nishida-Aoki¹,

Tominaga²,

et al. 2017

Self Cite

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show abstract

“…Results using the ExoScreen assay from the same group [22] showed that detection of CD145/CD9 dual positive cancer EVs is possible using 5 µL serum of colorectal cancer patients, and that EVs positive for GPRC5C/CD63 can discriminate pancreatitis patients from stage II pancreatic cancer. The assay is flexible for other cancer types also and examples of other cancer site-specific bead pairs were presented.…”

Section: General Perspectives On Ev Biomarkersmentioning

confidence: 99%

Summary of the ISEV workshop on extracellular vesicles as disease biomarkers, held in Birmingham, UK, during December 2017

Clayton

Buschmann

Byrd

et al. 2018

J of Extracellular Vesicle

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This report summarises the presentations and activities of the ISEV Workshop on extracellular vesicle biomarkers held in Birmingham, UK during December 2017. Among the key messages was broad agreement about the importance of biospecimen science. Much greater attention needs to be paid towards the provenance of collected samples. The workshop also highlighted clear gaps in our knowledge about pre-analytical factors that alter extracellular vesicles (EVs). The future utility of certified standards for credentialing of instruments and software, to analyse EV and for tracking the influence of isolation steps on the structure and content of EVs were also discussed. Several example studies were presented, demonstrating the potential utility for EVs in disease diagnosis, prognosis, longitudinal serial testing and stratification of patients. The conclusion of the workshop was that more effort focused on pre-analytical issues and benchmarking of isolation methods is needed to strengthen collaborations and advance more effective biomarkers.

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“…This is the case for Claudin, which is present only in exosomes derived from the plasma of women with ovarian cancer, 72 for Glypican-1 that appears to allow to distinguish an ovarian cancer with high specificity and sensitivity 56 or for CD9-CD147 that is embedded in colorectal cancer-derived exosomes. 73 It has also been reported that 80 percent of the exosomes isolated from NSCLC samples was positive for surface EGFR (epithelium growth factor receptor) by immune staining compared to only 2% of the exosomes in chronic inflammatory lung tissue. 74 Finally, as a general marker of cancer-derived exosomes, our team has recently proposed membrane HSP70 that is present in exosomes released by large panel of cancer cells but not by their normal counterparts 50 ; see below.…”

Section: Exosomes As Biomarkersmentioning

confidence: 97%

Exosomes in cancer theranostic: Diamonds in the rough

Cordonnier

Chanteloup

Isambert

et al. 2017

Cell Adhesion & Migration

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During the last 10 years, exosomes, which are small vesicles of 50-200 nm diameter of endosomal origin, have aroused a great interest in the scientific and clinical community for their roles in intercellular communication in almost all physiological and pathological processes. Most cells can potentially release these nanovesicles that share with the parent cell a similar lipid bilayer with transmembrane proteins and a panel of enclosed soluble proteins such as heat shock proteins and genetic material, thus acting as potential nanoshuttles of biomarkers. Exosomes surface proteins allow their targeting and capture by recipient cells, while the exosomes' content can modify the physiological state of recipient cells. Tumor derived exosomes by interacting with other cells of the tumor microenvironment modulate tumor progression, angiogenic switch, metastasis, and immune escape. Targeting tumor-derived exosomes might be an interesting approach in cancer therapy. Furthermore, because a key issue to improve cancer patients' outcome relies on earlier cancer diagnosis (metastases, as opposed to the primary tumor, are responsible for most cancer deaths) exosomes have been put forward as promising biomarker candidates for cancer diagnosis and prognosis. This review summarizes the roles of exosomes in cancer and clinical interest, focusing on the importance of exosomal heat shock proteins (HSP). The challenges of clinical translation of HSPexosomes as therapeutic targets and biomarkers for early cancer detection are also discussed.

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Ultra-sensitive liquid biopsy of circulating extracellular vesicles using ExoScreen

Cited by 481 publications

References 22 publications

Disruption of Circulating Extracellular Vesicles as a Novel Therapeutic Strategy against Cancer Metastasis

Disruption of Circulating Extracellular Vesicles as a Novel Therapeutic Strategy against Cancer Metastasis

Summary of the ISEV workshop on extracellular vesicles as disease biomarkers, held in Birmingham, UK, during December 2017

Exosomes in cancer theranostic: Diamonds in the rough

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