Article

Skog, J. et al. Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nature Cell Biol. 10, 1470-1476

Department of Neurology, Massachusetts General Hospital, and Neuroscience Program, Harvard Medical School, 149 13th Street, Charlestown, MA 02129, USA.
Nature Cell Biology (Impact Factor: 20.06). 12/2008; 10(12):1470-6. DOI: 10.1038/ncb1800
Source: PubMed

ABSTRACT Glioblastoma tumour cells release microvesicles (exosomes) containing mRNA, miRNA and angiogenic proteins. These microvesicles are taken up by normal host cells, such as brain microvascular endothelial cells. By incorporating an mRNA for a reporter protein into these microvesicles, we demonstrate that messages delivered by microvesicles are translated by recipient cells. These microvesicles are also enriched in angiogenic proteins and stimulate tubule formation by endothelial cells. Tumour-derived microvesicles therefore serve as a means of delivering genetic information and proteins to recipient cells in the tumour environment. Glioblastoma microvesicles also stimulated proliferation of a human glioma cell line, indicating a self-promoting aspect. Messenger RNA mutant/variants and miRNAs characteristic of gliomas could be detected in serum microvesicles of glioblastoma patients. The tumour-specific EGFRvIII was detected in serum microvesicles from 7 out of 25 glioblastoma patients. Thus, tumour-derived microvesicles may provide diagnostic information and aid in therapeutic decisions for cancer patients through a blood test.

Download full-text

Full-text

Available from: Dimphna Meijer, Jul 29, 2015
3 Followers
 · 
290 Views
  • Source
    • "FACS analysis of single cells obtained from vaginal tissues showed that human SE were internalized by murine vaginal cells in vivo within 24 h of inoculation (Fig. 4B). Following internalization, exosomes can donate functional mRNA to recipient cells (Kogure et al., 2011; Li et al., 2013; Skog et al., 2008). We used Apobec3G and Apobec3F TaqMan RT-qPCR to examine whether human SE donated Apobec3G and Apo- bec3F mRNA to mice. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Exosomes are membranous extracellular nanovesicles secreted by diverse cell types. Exosomes from healthy human semen have been shown to inhibit HIV-1 replication and to impair progeny virus infectivity. In this study, we examined the ability of healthy human semen exosomes to restrict HIV-1 and LP-BM5 murine AIDS virus transmission in three different model systems. We show that vaginal cells internalize exosomes with concomitant transfer of functional mRNA. Semen exosomes blocked the spread of HIV-1 from vaginal epithelial cells to target cells in our cell-to-cell infection model and suppressed transmission of HIV-1 across the vaginal epithelial barrier in our trans-well model. Our in vivo model shows that human semen exosomes restrict intravaginal transmission and propagation of murine AIDS virus. Our study highlights an antiretroviral role for semen exosomes that may be harnessed for the development of novel therapeutic strategies to combat HIV-1 transmission. Copyright © 2015 Elsevier Inc. All rights reserved.
    Virology 08/2015; 482. DOI:10.1016/j.virol.2015.03.040 · 3.28 Impact Factor
  • Source
    • "The use of electric fields, in combination with fluid flow, has been proposed as a powerful method to direct the behavior of vesicles towards a wide range of biotechnological applications. Weak electric fields have found applications in cell manipulation techniques such as electrofusion [31], tissue ablation [32], wound healing [33], and in the treatment of tumors [34]. Strong electric fields induce electro-poration in vesicles through the formation of transient pores in the membrane and could play a role in novel biotechnological advances such as the delivery of drugs and DNA into living cells [35] [36]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: A three-dimensional numerical model of vesicle electrohydrodynamics in the presence of DC electric fields is presented. The vesicle membrane is modeled as a thin capacitive interface through the use of a semi-implicit level set Jet scheme. The enclosed volume and surface area are conserved both locally and globally by a new Navier-Stokes projection method. The electric field calculations explicitly take into account the capacitive interface by an implicit Immersed Interface Method formulation, which calculates the electric potential field and the trans-membrane potential simultaneously. The results match well with previously published experimental, analytic and two-dimensional computational works.
    SIAM Journal on Scientific Computing 06/2015; 37(3):B473-B494. DOI:10.1137/140988966 · 1.94 Impact Factor
  • Source
    • "It has been shown that exosomes also contain RNA, in particular miRNA (more than 100 sequences ) and mRNA (more than 1300 sequences), some of which could be translated into proteins by target cells (Ratajczak et al. 2006; Valadi et al. 2007). Later studies reported on the RNA contents of vesicles isolated from other cell cultures (Skog et al. 2008) and from body fluids (Hunter et al. 2008; Rabinowits et al. 2009; Michael et al. 2010). Recent deep-sequencing experiments have shown that exosomes actually contain a very diverse RNA cargo, including hundreds of noncoding RNAs (snRNA, snoRNA, scaRNA, piRNA), tRNA, and rRNA (Schageman et al. 2013; Bellingham et al. 2012; Nolte-'t-Hoen et al. 2012). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Exosomes are tiny vesicles (diameter 30-150 nm) secreted by cells in culture and found in all body fluids. These vesicles, loaded with unique RNA and protein cargos, have many biological functions, of which only a small fraction is currently understood-for example, they participate in cell-to-cell communication and signaling within the human body. The spectrum of current scientific interest in exosomes is wide and ranges from understanding their functions and pathways to using them in diagnostics, as biomarkers, and in the development of therapeutics. Here we provide an overview of different strategies for isolation of exosomes from cell-culture media and body fluids. © 2015 Cold Spring Harbor Laboratory Press.
    Cold Spring Harbor Protocols 04/2015; 2015(4):pdb.top074476. DOI:10.1101/pdb.top074476 · 4.63 Impact Factor
Show more