Proteome characterization of melanoma exosomes reveals a specific signature for metastatic cell lines

Lazar, Ikrame; Clement, Emily; Ducoux-Petit, Manuelle; Denat, Laurence; Soldan, Vanessa; Dauvillier, Stéphanie; Balor, Stéphanie; Burlet‐Schiltz, Odile; Larue, Lionel; Müller, Cathérine; Nieto, Laurence

doi:10.1111/pcmr.12380

Cited by 132 publications

(142 citation statements)

References 38 publications

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“…[33][34][35] Apo-A1-CD63 presenting exosomes produced by 293T cells were loaded with miR-26a by electroporation and shown to be internalized by HepG2 cells via SR-B1 receptor-mediated endocytosis. The exosome-mediated delivery of miR-26a to HepG2 cells was further shown to upregulate miR-26a expression, where it downregulated key cell cycle proteins that arrested the cell cycle and inhibited cell proliferation.…”

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confidence: 99%

Engineered exosome-mediated delivery of functionally active miR-26a and its enhanced suppression effect in HepG2 cells

Liang

Kan

Zhu

et al. 2018

IJN

234

152

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Introduction Exosomes are closed-membrane nanovesicles that are secreted by a variety of cells and exist in most body fluids. Recent studies have demonstrated the potential of exosomes as natural vehicles that target delivery of functional small RNA and chemotherapeutics to diseased cells. Methods In this study, we introduce a new approach for the targeted delivery of exosomes loaded with functional miR-26a to scavenger receptor class B type 1-expressing liver cancer cells. The tumor cell-targeting function of these engineered exosomes was introduced by expressing in 293T cell hosts, the gene fusion between the transmembrane protein of CD63 and a sequence from Apo-A1. The exosomes harvested from these 293T cells were loaded with miR-26a via electroporation. Results The engineered exosomes were shown to bind selectively to HepG2 cells via the scavenger receptor class B type 1–Apo-A1 complex and then internalized by receptor-mediated endocytosis. The release of miR-26a in exosome-treated HepG2 cells upregulated miR-26a expression and decreased the rates of cell migration and proliferation. We also presented evidence that suggest cell growth was inhibited by miR-26a-mediated decreases in the amounts of key proteins that regulate the cell cycle. Conclusion Our gene delivery strategy can be adapted to treat a broad spectrum of cancers by expressing proteins on the surface of miRNA-loaded exosomes that recognize specific biomarkers on the tumor cell.

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mentioning

confidence: 99%

Engineered exosome-mediated delivery of functionally active miR-26a and its enhanced suppression effect in HepG2 cells

Liang

Kan

Zhu

et al. 2018

IJN

234

152

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“…Specimens were prepared as described previously (13). Mitochondria were quantified by counting the number per picture on at least 50 pictures per experiment (an average of 20 mitochondria per picture).…”

Section: Transmission Electron Microscopymentioning

confidence: 99%

“…When indicated, etomoxir (50 mmol/L) or trimetazidine (1 mmol/L) were added 24 hours after exosomes. Actin was stained with phalloidin as described previously (13).…”

Section: Cell Lines and Treatmentmentioning

confidence: 99%

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Adipocyte Exosomes Promote Melanoma Aggressiveness through Fatty Acid Oxidation: A Novel Mechanism Linking Obesity and Cancer

et al. 2016

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Malignant progression results from a dynamic cross-talk between stromal and cancer cells. Recent evidence suggests that this cross-talk is mediated to a significant extent by exosomes, nanovesicles secreted by most cell types and which allow the transfer of proteins, lipids, and nucleic acids between cells. Adipocytes are a major component of several tumor microenvironments, including that of invasive melanoma, where cells have migrated to the adipocyte-rich hypodermic layer of the skin. We show that adipocytes secrete exosomes in abundance, which are then taken up by tumor cells, leading to increased migration and invasion. Using mass spectrometry, we analyzed the proteome of adipocyte exosomes. Interestingly, these vesicles carry proteins implicated in fatty acid oxidation (FAO), a feature highly specific to adipocyte exosomes. We further show that, in the presence of adipocyte exosomes, FAO is increased in melanoma cells. Inhibition of this metabolic pathway completely abrogates the exosome-mediated increase in migration. Moreover, in obese mice and humans, both the number of exosomes secreted by adipocytes as well as their effect on FAO-dependent cell migration are amplified. These observations might in part explain why obese melanoma patients have a poorer prognosis than their nonobese counterparts. Cancer Res; 76(14); 4051-7. Ó2016 AACR.

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“…64 It was latter on reported that certain proteins were differentially expressed dependently on the melanoma cells from which the exosomes were analyzed, revealing a specific signature for metastatic cell lines. 65 In this way, in exosomes from patients with metastatic melanoma, MIA (Melanoma Inhibitory Activity) and S100B can be detected, therefore their quantification presents diagnostic and prognostic utility. 66 In 2015, Hoshino et al revealed that specific integrin expression in exosomes could be used to predict organ-specific metastasis.…”

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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Proteome characterization of melanoma exosomes reveals a specific signature for metastatic cell lines

Cited by 132 publications

References 38 publications

Engineered exosome-mediated delivery of functionally active miR-26a and its enhanced suppression effect in HepG2 cells

Engineered exosome-mediated delivery of functionally active miR-26a and its enhanced suppression effect in HepG2 cells

Adipocyte Exosomes Promote Melanoma Aggressiveness through Fatty Acid Oxidation: A Novel Mechanism Linking Obesity and Cancer

Exosomes in cancer theranostic: Diamonds in the rough

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