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Glioblastoma microvesicles transport RNA and proteins

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. The glioblastoma cell and exosome RNA was analyzed on two dual color arrays.

ORGANISM(S): Homo sapiens

SUBMITTER: Skog J

PROVIDER: S-ECPF-GEOD-13470 | biostudies-other | 2008 Dec

REPOSITORIES: biostudies-other

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Glioblastoma microvesicles transport RNA and proteins

Project description: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. The glioblastoma cell and exosome RNA was analyzed on two dual color arrays.

2008-11-15 | E-GEOD-13470 | biostudies-arrayexpress

Glioblastoma microvesicles transport RNA and proteins

2008-11-16 | GSE13470 | GEO

Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers.

| S-EPMC3423894 | biostudies-literature

RNA expression patterns in serum microvesicles from patients with glioblastoma multiforme and controls.

Project description:RNA from exosomes and other microvesicles contain transcripts of tumour origin. In this study we sought to identify biomarkers of glioblastoma multiforme in microvesicle RNA from serum of affected patients.Microvesicle RNA from serum from patients with de-novo primary glioblastoma multiforme (N = 9) and normal controls (N = 7) were analyzed by microarray analysis. Samples were collected according to protocols approved by the Institutional Review Board. Differential expressions were validated by qRT-PCR in a separate set of samples (N = 10 in both groups).Expression profiles of microvesicle RNA correctly separated individuals in two groups by unsupervised clustering. The most significant differences pertained to down-regulated genes (121 genes > 2-fold down) in the glioblastoma multiforme patient microvesicle RNA, validated by qRT-PCR on several genes. Overall, yields of microvesicle RNA from patients was higher than from normal controls, but the additional RNA was primarily of size < 500 nt. Gene ontology of the down-regulated genes indicated these are coding for ribosomal proteins and genes related to ribosome production.Serum microvesicle RNA from patients with glioblastoma multiforme has significantly down-regulated levels of RNAs coding for ribosome production, compared to normal healthy controls, but a large overabundance of RNA of unknown origin with size < 500 nt.

| S-EPMC3329625 | biostudies-literature

Characterization of single microvesicles in plasma from glioblastoma patients.

Project description:BackgroundExtracellular vesicles (EV) are shed by tumor cells but little is known about their individual molecular phenotypes and heterogeneity. While exosomes have received considerable attention, much less is known about larger microvesicles. Here we profile single microvesicles (MV) and exosomes from glioblastoma (GB) cells and MV from the plasma of patients.MethodsEV secreted from mouse glioma GL261 and human primary GBM8 cell lines as well as from the plasma of 8 patients with diagnoses of GB and 2 healthy controls were isolated and processed for single vesicle analysis. EV were immobilized on glass slides and the heterogeneity of vesicle and tumor markers were analyzed at the single vesicle level.ResultsWe show that (i) MV are abundant, (ii) only a minority of MV expresses putative MV markers, and (iii) MV share tetraspanin biomarkers previously thought to be diagnostic of exosomes. Using MV capture and staining techniques that allow differentiation of host cell and GB-derived MV we further demonstrate that (i) tumoral MV often present as <10% of all MV in GB patient plasma, and (ii) there is extensive heterogeneity in tumor marker expression in these tumor-derived MV.ConclusionThese results indicate that single MV analysis is likely necessary to identify rare tumoral MV populations and the single vesicle analytical technique used here can be applied to both MV and exosome fractions without the need for their separation from each other. These studies form the basis for using single EV analyses for cancer diagnostics.

| S-EPMC6502493 | biostudies-literature

Inducible Control of mRNA Transport Using Reprogrammable RNA-Binding Proteins.

Project description:Localization of mRNA is important in a number of cellular processes such as embryogenesis, cellular motility, polarity, and a variety of neurological processes. A synthetic device that controls cellular mRNA localization would facilitate investigations on the significance of mRNA localization in cellular function and allow an additional level of controlling gene expression. In this work, we developed the PUF (Pumilio and FBF homology domain)-assisted localization of RNA (PULR) system, which utilizes a eukaryotic cell's cytoskeletal transport machinery to reposition mRNA within a cell. Depending on the cellular motor used, we show ligand-dependent transport of mRNA toward either pole of the microtubular network of cultured cells. In addition, implementation of the reprogrammable PUF domain allowed the transport of untagged endogenous mRNA in primary neurons.

| S-EPMC5477001 | biostudies-literature

Protein typing of circulating microvesicles allows real-time monitoring of glioblastoma therapy.

Project description:Glioblastomas shed large quantities of small, membrane-bound microvesicles into the circulation. Although these hold promise as potential biomarkers of therapeutic response, their identification and quantification remain challenging. Here, we describe a highly sensitive and rapid analytical technique for profiling circulating microvesicles directly from blood samples of patients with glioblastoma. Microvesicles, introduced onto a dedicated microfluidic chip, are labeled with target-specific magnetic nanoparticles and detected by a miniaturized nuclear magnetic resonance system. Compared with current methods, this integrated system has a much higher detection sensitivity and can differentiate glioblastoma multiforme (GBM) microvesicles from nontumor host cell-derived microvesicles. We also show that circulating GBM microvesicles can be used to analyze primary tumor mutations and as a predictive metric of treatment-induced changes. This platform could provide both an early indicator of drug efficacy and a potential molecular stratifier for human clinical trials.

| S-EPMC3518564 | biostudies-literature

Endothelium-Released Microvesicles Transport miR-126 That Induces Proangiogenic Reprogramming in Monocytes.

Project description:We have recently shown that in ischemic tissue, the hypoxic endothelial cells (EC) release extracellular microvesicles (EMVs) that are rich in tissue factor (TF). These TF-EMVs induce monocyte (Mo) homing to the ischemic zone, their differentiation into EC-like cells, and the formation of new blood vessels increasing tissue perfusion. In addition to membrane proteins, EMVs contain noncoding RNAs that can modulate cellular signaling pathways in the recipient cells. Here, we have investigated whether miRNA contained into secreted EMVs may be transferred into Mo where they could modulate EC-like cell differentiation and angiogenic responses. Our results indicated that EMVs released from activated ECs contain high levels of miR-126 and that the levels are directly proportional to TF expression in EMVs. Interestingly, miR-126 is transferred to Mo when they are incubated with TF-EMVs. Increased levels of miR-126 in Mo do not promote EC-like cell differentiation but regulate angiogenesis by targeting several components of the VEGF pathway, as SPRED1 and PI3KR2. Our findings reveal that activated ECs secrete EMVs carrying miR-126, which can modulate Mo reprogramming of angiogenic genes.

| S-EPMC8894588 | biostudies-literature

RNA expression patterns in serum microvesicles from patients with glioblastoma multiforme and controls

Project description:Comparative expression analysis of RNA isolated from microvesicles from serum from glioblastoma multiforme (GBM) patients and normal healthy individuals.

2011-12-01 | GSE24084 | GEO

TooT-T: discrimination of transport proteins from non-transport proteins.

Project description:BACKGROUND:Membrane transport proteins (transporters) play an essential role in every living cell by transporting hydrophilic molecules across the hydrophobic membranes. While the sequences of many membrane proteins are known, their structure and function is still not well characterized and understood, owing to the immense effort needed to characterize them. Therefore, there is a need for advanced computational techniques takes sequence information alone to distinguish membrane transporter proteins; this can then be used to direct new experiments and give a hint about the function of a protein. RESULTS:This work proposes an ensemble classifier TooT-T that is trained to optimally combine the predictions from homology annotation transfer and machine-learning methods to determine the final prediction. Experimental results obtained by cross-validation and independent testing show that combining the two approaches is more beneficial than employing only one. CONCLUSION:The proposed model outperforms all of the state-of-the-art methods that rely on the protein sequence alone, with respect to accuracy and MCC. TooT-T achieved an overall accuracy of 90.07% and 92.22% and an MCC 0.80 and 0.82 with the training and independent datasets, respectively.

| S-EPMC7178945 | biostudies-literature

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