Metabolic reprogramming in transformed mouse cortical astrocytes: A proteomic study

Bentaïb, Azeddine; Tullio, Pascal De; Chneiweiss, Hervé; Hermans, Emmanuel; Junier, Marie‐Pierre; Leprince, Pierre

doi:10.1016/j.jprot.2014.09.019

Cited by 12 publications

(17 citation statements)

References 103 publications

(129 reference statements)

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“… 2D-DIGE analysis coupled with mass spectrometry is a global, without a priori, comparative proteomic approach particularly suited to identify and quantify enzymes isoforms and structural proteins, thus making it an efficient tool for the characterization of the changes in cell phenotypes that occur in physiological and pathological conditions. In this data article in support of the research article entitled “Metabolic reprogramming in transformed mouse cortical astrocytes: a proteomic study” [1] we illustrate the changes in protein profile that occur during the metabolic reprogramming undergone by cultured mouse astrocytes in a model of in-vitro cancerous transformation [2] . …”

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confidence: 77%

“…Using the 2D-DIGE approach we have obtained relevant information on the changes in abundance of most enzymes implicated in major canonical metabolic pathways [1] . Supplementary Table 1 lists all the identified proteins whose abundance differs by at least 1.5-fold ( p <0.05, student t -test) between normal astrocytes (NA) and transformed astrocytes (TA).…”

Section: Data Experimental Design Materials and Methodsmentioning

confidence: 99%

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Data in support of metabolic reprogramming in transformed mouse cortical astrocytes: A proteomic study

et al. 2015

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2D-DIGE analysis coupled with mass spectrometry is a global, without a priori, comparative proteomic approach particularly suited to identify and quantify enzymes isoforms and structural proteins, thus making it an efficient tool for the characterization of the changes in cell phenotypes that occur in physiological and pathological conditions. In this data article in support of the research article entitled “Metabolic reprogramming in transformed mouse cortical astrocytes: a proteomic study” [1] we illustrate the changes in protein profile that occur during the metabolic reprogramming undergone by cultured mouse astrocytes in a model of in-vitro cancerous transformation [2].

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confidence: 77%

Section: Data Experimental Design Materials and Methodsmentioning

confidence: 99%

Data in support of metabolic reprogramming in transformed mouse cortical astrocytes: A proteomic study

et al. 2015

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“…Interestingly we observed a slight reduction in pyruvate kinase M2 (PKM2; 0.92 fold), the PK isoform that is often associated with tumor specific expression and aerobic glycolysis ( 43 ). The role of PKM2 in hypoxic glycolysis is however less clear and recent data suggests that the regulation of PKM1 and PKM2 isoforms in cancer may be more complicated than originally thought ( 44 – 46 ).…”

Section: Discussionmentioning

confidence: 99%

Targeted Proteomics to Assess the Response to Anti-Angiogenic Treatment in Human Glioblastoma (GBM)

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Duriez

et al. 2016

Molecular & Cellular Proteomics

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Glioblastoma (GBM) is a highly aggressive primary brain tumor with dismal outcome for affected patients. Because of the significant neo-angiogenesis exhibited by GBMs, anti-angiogenic therapies have been intensively evaluated during the past years. Recent clinical studies were however disappointing, although a subpopulation of patients may benefit from such treatment. We have previously shown that anti-angiogenic targeting in GBM increases hypoxia and leads to a metabolic adaptation toward glycolysis, suggesting that combination treatments also targeting the glycolytic phenotype may be effective in GBM patients. The aim of this study was to identify marker proteins that are altered by treatment and may serve as a short term readout of anti-angiogenic therapy. Ultimately such proteins could be tested as markers of efficacy able to identify patient subpopulations responsive to the treatment. We applied a proteomics approach based on selected reaction monitoring (SRM) to precisely quantify targeted protein candidates, selected from pathways related to metabolism, apoptosis and angiogenesis. The workflow was developed in the context of patient-derived intracranial GBM xenografts developed in rodents and ensured the specific identification of human tumor versus rodent stroma-derived proteins. Quality control experiments were applied to assess sample heterogeneity and reproducibility of SRM assays at different levels. The data demonstrate that tumor specific proteins can be precisely quantified within complex biological samples, reliably identifying small concentration differences induced by the treatment. In line with previous work, we identified decreased levels of TCA cycle enzymes, including isocitrate dehydrogenase, whereas malectin, calnexin, and lactate dehydrogenase A were augmented after treatment. We propose the most responsive proteins of our subset as potential novel biomarkers to assess treatment response after anti-angiogenic therapy that warrant future analysis in clinical GBM samples.

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“…Our approach was to investigate a possible link between cellularity and the NOE-contrast in tumors which is based on the assumption that protein metabolism is a crucial factor for glioblastoma cells. It is known that significant metabolic reprogramming occurs in astrocytes as they turn malignant, for example the abundance of enzymes responsible for protein synthesis, processing and degradation varies in comparison to normal astrocytes [ 13 , 14 ]. Consequently, the expressed proteins in glioblastoma cells differ significantly from those in normal astrocytes [ 15 ] which might influence the NOE-signal in areas of condensed tumor cells.…”

Section: Introductionmentioning

confidence: 99%

Nuclear Overhauser Enhancement Imaging of Glioblastoma at 7 Tesla: Region Specific Correlation with Apparent Diffusion Coefficient and Histology

et al. 2015

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ObjectiveTo explore the correlation between Nuclear Overhauser Enhancement (NOE)-mediated signals and tumor cellularity in glioblastoma utilizing the apparent diffusion coefficient (ADC) and cell density from histologic specimens. NOE is one type of chemical exchange saturation transfer (CEST) that originates from mobile macromolecules such as proteins and might be associated with tumor cellularity via altered protein synthesis in proliferating cells.Patients and MethodsFor 15 patients with newly diagnosed glioblastoma, NOE-mediated CEST-contrast was acquired at 7 Tesla (asymmetric magnetization transfer ratio (MTRasym) at 3.3ppm, B1 = 0.7 μT). Contrast enhanced T1 (CE-T1), T2 and diffusion-weighted MRI (DWI) were acquired at 3 Tesla and coregistered. The T2 edema and the CE-T1 tumor were segmented. ADC and MTRasym values within both regions of interest were correlated voxelwise yielding the correlation coefficient rSpearman (rSp). In three patients who underwent stereotactic biopsy, cell density of 12 specimens per patient was correlated with corresponding MTRasym and ADC values of the biopsy site.ResultsEight of 15 patients showed a weak or moderate positive correlation of MTRasym and ADC within the T2 edema (0.16≤rSp≤0.53, p<0.05). Seven correlations were statistically insignificant (p>0.05, n = 4) or yielded rSp≈0 (p<0.05, n = 3). No trend towards a correlation between MTRasym and ADC was found in CE-T1 tumor (-0.310.05, n = 6). The biopsy-analysis within CE-T1 tumor revealed a strong positive correlation between tumor cellularity and MTRasym values in two of the three patients (rSp patient3 = 0.69 and rSp patient15 = 0.87, p<0.05), while the correlation of ADC and cellularity was heterogeneous (rSp patient3 = 0.545 (p = 0.067), rSp patient4 = -0.021 (p = 0.948), rSp patient15 = -0.755 (p = 0.005)).DiscussionNOE-imaging is a new contrast promising insight into pathophysiologic processes in glioblastoma regarding cell density and protein content, setting itself apart from DWI. Future studies might be based on the assumption that NOE-mediated CEST visualizes cellularity more accurately than ADC, especially in the CE-T1 tumor region.

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Metabolic reprogramming in transformed mouse cortical astrocytes: A proteomic study

Cited by 12 publications

References 103 publications

Data in support of metabolic reprogramming in transformed mouse cortical astrocytes: A proteomic study

Data in support of metabolic reprogramming in transformed mouse cortical astrocytes: A proteomic study

Targeted Proteomics to Assess the Response to Anti-Angiogenic Treatment in Human Glioblastoma (GBM)

Nuclear Overhauser Enhancement Imaging of Glioblastoma at 7 Tesla: Region Specific Correlation with Apparent Diffusion Coefficient and Histology

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