C2C12 myoblasts release micro-vesicles containing mtDNA and proteins involved in signal transduction

Guescini, Michele; Guidolin, Diego; Vallorani, Luciana; Casadei, Lucia; Gioacchini, Anna Maria; Tibollo, Pasquale; Battistelli, Michela; Falcieri, Elisabetta; Battistin, Leontino; Agnati, Luigi F.; Stocchi, Vilberto

doi:10.1016/j.yexcr.2010.04.006

Cited by 258 publications

(233 citation statements)

References 49 publications

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“…However, the presence of DNA in exosomes is largely undetermined (21). Two previous studies have shown that exosomes contain mitochondrial DNA, single-stranded DNA, and transposable elements (13,14). Our study provides evidence that exosomes can carry large fragments (Ͼ10 kb) of double-stranded genomic DNA, apart from mitochondrial DNA and small amounts of singlestranded DNA (13,14).…”

Section: Discussionmentioning

confidence: 52%

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Identification of Double-stranded Genomic DNA Spanning All Chromosomes with Mutated KRAS and p53 DNA in the Serum Exosomes of Patients with Pancreatic Cancer

Kahlert

Melo

Protopopov

et al. 2014

Journal of Biological Chemistry

871

741

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Background: Exosomes are small vesicles in the tumor microenvironment containing nucleic acids and proteins with the capacity to influence cell behavior. Results: Exosomes contain double-stranded genomic DNA. Conclusion: Exosomes have the capacity to carry and transport genomic DNA spanning all chromosomes with KRAS and p53 mutations. Significance: Exosomes can aid in identifying genomic mutations in patients with pancreatic cancer.

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Section: Discussionmentioning

confidence: 52%

“…It has been reported that exosomes from astrocytes and glioblastoma cells carry mitochondrial DNA (13). Furthermore, it has been shown that exosomes from glioblastoma cell lines contain small amounts of single-stranded DNA as well as high levels of transposable elements (14).…”

mentioning

confidence: 99%

Identification of Double-stranded Genomic DNA Spanning All Chromosomes with Mutated KRAS and p53 DNA in the Serum Exosomes of Patients with Pancreatic Cancer

Kahlert

Melo

Protopopov

et al. 2014

Journal of Biological Chemistry

871

741

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“…We performed differential centrifugation coupled with membrane filtration in order to eliminate large contaminating extracellular vesicles, though small contaminating vesicles may still have been present in the preparation (12).…”

Section: Membrane Nanotubes and Microvesiclesmentioning

confidence: 99%

Flow cytometric analyses disclose intercellular communications in FasL‐stimulated T cells: Results and trouble shooting

et al. 2011

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LIFE depends on the ability of cells to communicate with one another. Much of this crosstalk occurs at cell-cell contacts and is regulated by complex structural interface: neurological and immunological synapses that transmit cell-cell signals through the extracellular space, relying on mechanisms of ligand-receptor signalling across tight cell-cell junctions. In addition to these well-known examples, other cellular structures involved in cell-cell communication have been identified (1). A frequent result of cell-cell communication is collective population behavior that can potentially lead to complex phenotypes not observed in separate individual cells, for example, in development or tumor formation (2,3). Immune responses against pathogens or any foreign antigens require fine immune regulation, where cellular communications are mediated by either soluble or cell surface molecules. Generally, absorption, exosome production and uptake, internalization, and membrane nanotube formation are the probable mechanisms through which the membrane fragments and cytoplasmic content are transferred from one cell to another (4). The identification of new structures involved in cell-to-cell communication has led to the development of new analytical and imaging tools, which have allowed us to enhance our understanding of the ubiquitous phenomenon of cell-to-cell communication. Such tools include quantitative cell microscopy, now mainly represented by two distinct techniques: flow cytometry (FCM) and image cytometry (IC) (5). FCM allows analysis of cell suspensions, cell-by-cell quantification of optical signals, rapid analysis (several hundred cells per second), and cell sorting, whereas IC allows precise localization and quantification of optical signals emitted by each point of the observed field and image analysis (morphology and morphometry). FASL STIMULATION OF T CELLSThe Fas/CD95 surface receptor mediates rapid death of various cell types, including autoreactive T cells, which can trigger autoimmunity. In this study we investigate novel aspects of Fas signaling that define a ''social'' dimension to receptor-induced apoptosis. At least in some cell types, FasL can be stored in granules and then rapidly released at the cell surface in response to external stimuli. Alternatively, FasL can be cleaved from the membrane by matrix metalloproteases and act as a soluble cytokine (6). In its membrane-bound form, FasL acts as a ligand for Fas and can trigger Fas-induced death.In our experiments, CD41 T cells were purified from PBMC by negative selection using the MACS system. CD41 T cells and Jurkat cells were both treated with FasL at a final concentration of 0.5 lg/ml for a maximum of 2 h. Our previous findings (7) showed that Fas stimulation led to an intriguing (and previously unsuspected) asymmetry of death propagation according to cell conjugation and rapidly induced extensive membrane nanotube formation between neighboring T cells. The experiments were performed using flow cytometric (FC) and morphologic (fluorescence and ti...

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“…However, some contradictory reports exist pointing out that the presence of DNA might be dependent on the source of analyzed exosomes. For instance, it has been claimed that glioblastoma and astrocytoma cell-released exosomes might carry mitochondrial DNA (Guescini et al , 2010 ). Since the first report demonstrating the presence of mRNA and microRNA in exosome preparations (Valadi et al , 2007 ), thousands of different mRNAs may be identified in exosomes derived from murine and human cells.…”

Section: Nucleic Acidsmentioning

confidence: 99%

Exosomes: the ideal nanovectors for biodelivery

Fais

Logozzi

Lugini

et al. 2012

Biological Chemistry

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Nanomedicine aims to exploit the improved and often novel physical, chemical, and biological properties of materials at the nanometric scale, possibly with the highest level of biomimetism, an approach that simulates what occurs in nature. Although extracellularly released vesicles include both microvesicles (MVs) and exosomes, only exosomes have the size that may be considered suitable for potential use in nanomedicine. In fact, recent reports have shown that exosomes are able to interact with target cells within an organ or at a distance using different mechanisms. Much is yet to be understood about exosomes, and currently, we are looking at the visible top of an iceberg, with most of what we have to understand on these nanovesicles still under the sea. In fact, we know that exosomes released by normal cells always trigger positive effects, whereas those released by cells in pathological condition, such as tumor or infected cells, may induce undesired, dangerous, and mostly unknown effects, but we cannot exclude the possibility that exosomes may also be detrimental for the body in normal conditions. However, whether we consider extracellular vesicles as a whole, thus including MVs, it appears that even in normal conditions, extracellular vesicles may lead to unwanted effects, depending on gender and age. This review aims to critically emphasize existing data in the literature that support the possible roles of exosomes in both diagnostic and therapeutic scopes.

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C2C12 myoblasts release micro-vesicles containing mtDNA and proteins involved in signal transduction

Cited by 258 publications

References 49 publications

Identification of Double-stranded Genomic DNA Spanning All Chromosomes with Mutated KRAS and p53 DNA in the Serum Exosomes of Patients with Pancreatic Cancer

Identification of Double-stranded Genomic DNA Spanning All Chromosomes with Mutated KRAS and p53 DNA in the Serum Exosomes of Patients with Pancreatic Cancer

Flow cytometric analyses disclose intercellular communications in FasL‐stimulated T cells: Results and trouble shooting

Exosomes: the ideal nanovectors for biodelivery

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