C6 glioma-derived microvesicles stimulate the proliferative and metastatic gene expression of normal astrocytes

Taheri, Behnaz; Soleimani, Masoud; Aval, Sedigheh Fekri; Memari, Fatemeh; Zarghami, Nosratollah

doi:10.1016/j.neulet.2018.08.034

Cited by 18 publications

(15 citation statements)

References 25 publications

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“…4 Accordingly, EVs can initiate thrombin generation and clot propagation but also activate fibrinolysis by providing a catalytic surface for plasmin generation. 5 EVs have also been associated with malignant proliferation by affecting the expression of genes involved in tumor invasion, 6 although these results have yet to be confirmed.…”

Section: Introductionmentioning

confidence: 99%

Processing methods and storage duration impact extracellular vesicle counts in red blood cell units

et al. 2020

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Extracellular vesicles (EVs) are active components of red blood cell (RBC) concentrates and may be associated with beneficial and adverse effects of transfusion. Elucidating controllable factors associated with EV release in RBC products is thus important to better manage the quality and properties of RBC units. Erythrocyte-derived EVs (EEVs) and platelet-derived EVs (PEVs) were counted in 1226 RBC units (administered to 280 patients) using a standardized cytometry-based method. EV size and CD47 and annexin V expression were also measured. The effects of donor characteristics, processing methods, and storage duration on EV counts were analyzed by using standard comparison tests, and analysis of covariance was used to determine factors independently associated with EV counts. PEV as well as EEV counts were higher in whole-blood–filtered RBC units compared with RBC-filtered units; PEV counts were associated with filter type (higher with filters associated with higher residual platelets), and CD47 expression was higher on EEVs in RBC units stored longer. Multivariate analysis showed that EEV counts were strongly associated with filter type (P < .0001), preparation, and storage time (+25.4 EEV/µL per day [P = .01] and +42.4 EEV/µL per day [P < .0001], respectively). The only independent factor associated with PEV counts was the residual platelet count in the unit (+67.1 PEV/µL; P < .0001). Overall, processing methods have an impact on EV counts and characteristics, leading to large variations in EV quantities transfused into patients. RBC unit processing methods might be standardized to control the EV content of RBC units if any impacts on patient outcomes can be confirmed. The IMIB (Impact of Microparticles in Blood) study is ancillary to the French ABLE (Age of Transfused Blood in Critically Ill Adults) trial (ISRCTN44878718).

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Section: Introductionmentioning

confidence: 99%

Processing methods and storage duration impact extracellular vesicle counts in red blood cell units

et al. 2020

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“…We used two different concentrations of EVs (7.5 and 15 μg/mL) to assess a dose-dependent effect on these cells due to the EVs. EV concentrations were chosen on the basis of previous observations described in the literature [18,19,25]. After three days of incubation, cells were stained with anti-GFAP, anti-MAP2 and anti-nestin antibodies (Figure 3).…”

Section: Resultsmentioning

confidence: 99%

“…In our experiments, EV treatment seemed to stimulate cells to differentiate, addressing target cells toward an astrocytic phenotype. In the literature, an opposite effect has recently been described, where exosomes produced by C6 glioma cells instead stimulated cell proliferation when incubated with primary cultures of rat cortical astrocytes [25]. The reason for such an opposite effect may reside in the cells of origin of the exosomes: It is likely that C6 glioma cells, being a tumor, may stimulate proliferation in order to increase the number of cells that invade the tissue.…”

Section: Discussionmentioning

confidence: 99%

Extracellular Vesicle-Induced Differentiation of Neural Stem Progenitor Cells

Stronati

Conti

Cacci

et al. 2019

IJMS

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Neural stem progenitor cells (NSPCs) from E13.5 mouse embryos can be maintained in culture under proliferating conditions. Upon growth-factor removal, they may differentiate toward either neuronal or glial phenotypes or both. Exosomes are small extracellular vesicles that are part of the cell secretome; they may contain and deliver both proteins and genetic material and thus play a role in cell–cell communication, guide axonal growth, modulate synaptic activity and regulate peripheral nerve regeneration. In this work, we were interested in determining whether NSPCs and their progeny can produce and secrete extracellular vesicles (EVs) and if their content can affect cell differentiation. Our results indicate that cultured NSPCs produce and secrete EVs both under proliferating conditions and after differentiation. Treatment of proliferating NSPCs with EVs derived from differentiated NSPCs triggers cell differentiation in a dose-dependent manner, as demonstrated by glial- and neuronal-marker expression.

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“…Unlike the papers described above, a recent study of human glioblastoma exosome-like EVs incubated with human astrocytes showed a dramatic proinflammatory response from the astrocytes—whose conditioned medium drove glioblastoma cell proliferation—and also prosurvival tumor-like signaling pathways that promoted astrocyte growth in soft agar (103). Using the rat C6 glioma line, Taheri et al(136) also found that C6 EV (microvesicles 200–300 nm in diameter) treatment of rat astrocytes stimulated astrocyte proliferation and GFAP mRNA expression and also upregulated mRNA expression of the matrix metalloproteinases MMP2 and MMP14 (with no effect on MMP9 mRNA, and downregulation of TIMP2). Further studies of glioblastoma EVs (exosome-like EVs) and astrocytes indeed demonstrated gelatinase activity from astrocytes treated with glioblastoma EVs (47), which is consistent with the astrocyte MMP9 release seen by Oushy et al (103).…”

Section: An Overview Of Research On Extracellular Vesicles In Brain Tmentioning

confidence: 97%

Roles of Extracellular Vesicles in High-Grade Gliomas: Tiny Particles with Outsized Influence

Graner

2019

Annu. Rev. Genom. Hum. Genet.

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High-grade gliomas, particularly glioblastomas (grade IV), are devastating diseases with dismal prognoses; afflicted patients seldom live longer than 15 months, and their quality of life suffers immensely. Our current standard-of-care therapy has remained essentially unchanged for almost 15 years, with little new therapeutic progress. We desperately need a better biologic understanding of these complicated tumors in a complicated organ. One area of rejuvenated study relates to extracellular vesicles (EVs)—membrane-enclosed nano- or microsized particles that originate from the endosomal system or are shed from the plasma membrane. EVs contribute to tumor heterogeneity (including the maintenance of glioma stem cells or their differentiation), the impacts of hypoxia (angiogenesis and coagulopathies), interactions amid the tumor microenvironment (concerning the survival of astrocytes, neurons, endothelial cells, blood vessels, the blood–brain barrier, and the ensuing inflammation), and influences on the immune system (both stimulatory and suppressive). This article reviews glioma EVs and the ways that EVs manifest themselves as autocrine, paracrine, and endocrine factors in proximal and distal intra- and intercellular communications. The reader should note that there is much controversy, and indeed confusion, in the field over the exact roles for EVs in many biological processes, and we will engage some of these difficulties herein.

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C6 glioma-derived microvesicles stimulate the proliferative and metastatic gene expression of normal astrocytes

Cited by 18 publications

References 25 publications

Processing methods and storage duration impact extracellular vesicle counts in red blood cell units

Processing methods and storage duration impact extracellular vesicle counts in red blood cell units

Extracellular Vesicle-Induced Differentiation of Neural Stem Progenitor Cells

Roles of Extracellular Vesicles in High-Grade Gliomas: Tiny Particles with Outsized Influence

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