Regulation of exosome release from mammary epithelial and breast cancer cells – A new regulatory pathway

Riches, Andrew; Campbell, Elaine C.; Borger, Eva; Powis, Simon J.

doi:10.1016/j.ejca.2013.12.019

Cited by 220 publications

(168 citation statements)

References 33 publications

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“…In our study model, B cells showed a high level of uptake, possibly due to the B cell origin of the lymphoma exosomes, supporting the idea of uptake specificity given the exosomes were collected primarily from cells originating from B cell lymphoma disease. These findings are in line with those of Hazan-Halevy et al 45 and Gutzeit et al 54 concerning B cells and Riches et al 55 in their work with breast tissue. In this study, we observed that DLCL2 exosomes were taken up rapidly and preferentially into CD19+ B lymphocytes and CD14+ monocytes.…”

supporting

confidence: 82%

Uptake of lymphoma-derived exosomes by peripheral blood leukocytes

Bennit¹,

Gonda²,

Oppegard³

et al. 2017

BLCTT

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Exosomes are nanosized lipid vesicles secreted into blood and other body fluids and serve as vehicles for intercellular communication. Despite being an important component of the tumor microenvironment (TME), exosomal targeting and uptake into recipient cells are still not fully understood. Few studies have looked at lymphoma exosomes and their interactions with circulating blood cells. In this study, we examine the exosomal uptake distribution among peripheral blood leukocytes (PBLs) using vesicles derived from a diffuse large B cell lymphoma cell line, WSU-DLCL2. Lymphoma cells survive, proliferate, and are protected from the cytotoxic effects of chemotherapeutic agents by soluble factors or by direct contact with inflammatory and stromal cells within the TME. In an attempt to close the gap in knowledge concerning lymphoma TME immunosuppression, we have treated normal human PBLs with PKH67-labeled lymphoma exosomes and monitored the uptake by measuring fluorescence at different time points using flow cytometry and fluorescent microscopy. Our results show that of the four populations examined, B cells and monocytes demonstrated uptake of PKH67-labeled exosomes, while T cells and NK cells displayed significantly less uptake.

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supporting

confidence: 82%

Uptake of lymphoma-derived exosomes by peripheral blood leukocytes

Bennit¹,

Gonda²,

Oppegard³

et al. 2017

BLCTT

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“…Exosomes derived from a bladder cancer cell line (SW780 cells) are internalized by cancer cells [30]. We have also shown that human breast cancer cells also internalize exosomes derived from human breast cancer lines and also from normal human mammary epithelial cells [4]. The release of exosomes from both normal cells and breast cancer cells is regulated by the presence of exosomes from these cells in the extracellular environment.…”

Section: Discussionmentioning

confidence: 74%

“…These vesicles contain proteins and RNA species and characteristic cell surface markers. Nanoparticle tracking analysis (NTA) has been widely used to determine the size profiles and concentrations of exosomes derived from both normal and tumor cells in culture [3,4]. Exosomes have a wide range of biological activity capable of modulating the immune response [5], inducing angiogenesis [6], modulating niche formation in metastasis [7] and influencing tumor growth [8,9].…”

Section: Introductionmentioning

confidence: 99%

Human urinary exosomes in bladder cancer patients: properties, concentrations and possible clinical application

Riches¹,

Powis²,

Mullen³

et al. 2015

Bladder

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OBJECTIVE:High grade bladder cancer is extremely aggressive. Early detection is thus an important challenge. Development of non-invasive diagnostic tools particularly using urine samples could be of importance in the diagnosis and surveillance of these patients. Exosomes are small vesicles present in the urine and have the potential to be used as biomarkers of cancer. Thus studies of the properties and concentrations of these particles in bladder cancer patients are of importance. MATERIALS AND METHODS:The concentration of exosomes present in urine was determined by nanoparticle tracking analysis using a Nanosight LM10 unit. Clinical urine samples were routinely collected and fixed using Preservcyt. The morphology of exosomes was studied in electron micrographs and characteristic exosome markers using Western blots. RESULTS:The exosome concentration of fixed samples stored at room temperature was constant for 48 hours and the same as fresh samples. Exosomes derived from patients presenting for a transurethral resection of their bladder tumor exhibited the exosome markers ALIX and TSG101 and also the classic cup shaped appearance in electron micrographs. The concentration of exosomes in patients presenting for transurethral resection of a bladder tumor was significantly greater than in patients presenting for check cystoscopy with no recurrence (median 77.2 × 10 8 per ml compared with 38.8 × 10 8 per ml, P < 0.001). A ROC analysis (area under the curve 77.4%) suggested that a suitable cut-off concentration of 85 × 10 8 per ml is associated with a sensitivity of 43% and specificity of 91% for diagnosing bladder cancer. CONCLUSIONS:Thus the concentration and properties of exosomes can be conveniently studied in fixed urine samples derived from bladder cancer patients. The characteristic properties of exosomes were preserved and increased numbers were found in patients presenting for transurethral resection of their tumor. With an appropriate cut-off value, urinary exosome concentrations may have utility in excluding a cancer recurrence when monitoring patients successfully treated for bladder cancer.

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“…59 They are great potential tools for providing noninvasive, sensitive and economically justifiable new diagnosis methods in oncology. 60 The main advantage of quantifying tumor-derived exosomes compared to circulating tumor cells (CTCs) is that exosomes are found in large amounts compared to CTCs (e.g : 53.2 § 1.6 £ 10 8 exosomes per 10 6 cells in the 24 h period, determined by Nanoparticle Tracking Analysis, Nanosight LM10, 61 Furthermore, exosomes can be quantified non-invasively in urines and other human fluids.…”

Section: Exosomes As Biomarkersmentioning

confidence: 99%

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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Regulation of exosome release from mammary epithelial and breast cancer cells – A new regulatory pathway

Cited by 220 publications

References 33 publications

Uptake of lymphoma-derived exosomes by peripheral blood leukocytes

Uptake of lymphoma-derived exosomes by peripheral blood leukocytes

Human urinary exosomes in bladder cancer patients: properties, concentrations and possible clinical application

Exosomes in cancer theranostic: Diamonds in the rough

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