Exosomes from CD99-deprived Ewing sarcoma cells reverse tumor malignancy
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Manuela Ferracin
PROVIDER: E-MTAB-7585 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:Ewing sarcoma (EWS) is an aggressive pediatric bone tumor characterized by unmet clinical needs and an incompletely understood epigenetic heterogeneity. Here we considered CD99, a major surface molecule hallmark of EWS malignancy. Fluctuations of CD99 expression strongly impair cell dissemination, differentiation, and death. CD99 is also loaded within extracellular vesicles (EVs) and the delivery of CD99 positive or CD99 negative EVs dynamically exerts oncogenic or oncosuppressive functions to recipient cells, respectively. We undertook mass spectrometry and functional annotation analysis to investigate the consequences of CD99 silencing on the proteomic landscape of EWS cells and related EVs. Our data demonstrate that i. the decrease of CD99 leads to major changes in the proteomic profile of EWS cells and EVs; ii. intracellular and extracellular compartments display two distinct signatures of differentially expressed proteins; iii. proteomic changes converge to the modulation of cell migration and immune-modulation biological processes; iv. CD99-silenced cells and related EVs are characterized by a migration-suppressive, pro-immunostimulatory proteomic profile. Overall, our data provide a novel source of CD99-associated protein biomarkers to be considered for further validation as mediators of EWS malignancy and as EWS disease liquid biopsy markers.
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Project description:Hypoxia is a low oxygen condition that occurs in the developing tumor mass and that is associated with poor prognosis and resistance to chemo- and radio-therapy. The definition of the hypoxia gene signature is fundamental for the understanding of tumor biology, as in the case of neuroblastoma, the most common pediatric solid tumor. The issue of identifying a significant group of variables in microarray gene expression experiments is particularly difficult due to the typical high dimensional nature of the data and great effort has been spent in the development of feature selection techniques. Our main goal is to define a robust hypoxia gene signature in neuroblastoma cell lines. A set of 11 neuroblastoma cell lines were cultured under normoxic and hypoxic conditions for 18 hours, and their gene expression profiles were measured with Affymetrix GeneChip HG-U133 Plus 2.0. We used the l1-l2 regularization framework in order to select the significant probesets defining hypoxic versus normoxic cell lines. Experiment Overall Design: The expression profiles of 11 neuroblastoma cell lines under normoxia vs hypoxia were studied.
2009-10-10 | E-GEOD-17714 | biostudies-arrayexpress
Project description:Hypoxia is a low oxygen condition that occurs in the developing tumor mass and that is associated with poor prognosis and resistance to chemo- and radio-therapy. The definition of the hypoxia gene signature is fundamental for the understanding of tumor biology, as in the case of neuroblastoma, the most common pediatric solid tumor. The issue of identifying a significant group of variables in microarray gene expression experiments is particularly difficult due to the typical high dimensional nature of the data and great effort has been spent in the development of feature selection techniques. Our main goal is to define a robust hypoxia gene signature in neuroblastoma cell lines. A set of 9 neuroblastoma cell lines were cultured under normoxic and hypoxic conditions for 18 hours, and their gene expression profiles were measured with Affymetrix GeneChip HG-U133 Plus 2.0. The clustering analysis of the expression profiles based on different clustering methods consistently revealed that hypoxia was not the major factor characterizing the data set. T-test analysis with multiple testing correction fails to identify significantly differentially expressed genes. Conversely the l1-l2 regularization selects 11 significant probesets while building an effective classification rule. The algorithm is cast within a cross-validation framework in order to achieve an unbiased analysis. The estimated cross-validation error is 17% (3 out of 18). We show that the use of l1-l2 regularization allowed us to model the effect of hypoxia, which was not detected by conventional t-test based approaches and we find a panel of genes able to properly discriminate the normoxic versus the hypoxic status of neuroblastoma cell lines. Experiment Overall Design: The expression profile of 9 neuroblastoma cell lines under normoxia vs hypoxia was studied
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Project description:Tumor chemoresistance is often associated to high aerobic glycolysis rates and reduced oxidative phosphorylation by cancer cells, a phenomenon called the “Warburg effect”. Thus, a treatment reversing the Warburg effect could decrease tumor cell survival both in the presence or absence of chemotherapy. Short-term starvation (STS) could accomplish this task since it is accompanied by a glucose and amino acid decrease and fatty acid increase, which require respiration for energy production. We tested the cytotoxicity of STS+Oxaliplatin on colon cancer cells by Trypan Blue, Carboxyfluorescein Succinimidyl ester and Annexin V staining. Reactive oxygen species production was measured by 2',7'-dichlorodihydrofluorescein diacetate staining. In vitro glucose consumption was evaluated by 18F-Fluoro-deoxyglucose uptake. Gene expression was tested by microarray analysis. Protein expression and activity were studied by western blot, proteomic analyses and spectrophotometric assays. CT26 bearing mice consumed only water for 48 hours (STS) before oxaliplatin treatment. Dynamic micro-Positron Emission Tomography and tumor growth measurements were performed. STS+Oxaliplatin cause a potent suppression of colon carcinoma growth and glucose consumption in in vitro and in vivo models. In CT26 cells, STS down-regulates aerobic glycolysis, and glutaminolysis, while increasing oxidative phosphorylation. STS-dependent increase in O2 consumption is associated with reduced ATP synthesis and increased oxidation. In combination with chemotherapy, these effects of STS cause additive toxicity to cancer cells. Our findings indicate that during and following STS the decreased glucose levels promote an anti-Warburg effect characterized by increased oxygen consumption but failure to generate ATP, resulting in oxidative damage and apoptosis. The experiment comprised for conditions: Control, Starvation, Oxaliplatin, and Starvation plus Oxaliplatin
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Project description:In animal models and human trials, intramyocardial injection of adult bone-marrow derived mesenchymal stem cells (BM-MSC) provides beneficial effects in failing hearts. These effects are mainly mediated through paracrine mechanisms. Mesenchymal stem cells of fetal origin (hAMC) can be isolated from the amniotic membrane of human placenta. Our results provide evidence that hAMC exert remarkable cardioprotective effects through paracrine mechanisms. However, the complete nature and scope of the paracrine mediators of cardioprotection have not been investigated yet. We compared the gene expression profiling of hAMC (n=8), BM-MSC (n=10) and dermal fibroblasts (n=6) to shed light onto the identity of putative cardioprotective factors secreted by fetal MSC. Total RNA was extracted from cultured hAMC (n=8), BM-MSC (n=10) and dermal fibroblasts (n=6) and analyzed with HumanHT-12 v3 Expression BeadChips
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Project description:Ewing's Sarcoma cell lines were made resistant to different IGF-1R drugs to investigate mechanisms and pathways modulated by the resistance. EWS TC-71 cell line was exposed to increasing concentration to three different anti-IGF-1R drugs (HAb AVE1642, TKI NVP-AEW541, HAb CP-751,871, cell lines named respectively as TC/AVE, TC/AEW or TC/CP) for at least six months. Expression profile of resistant cell variants was compared either singularly for each resistance or commonly vs. parental cell line. Two technical replicates for resistant variants and three biological replicated for parental cell were present.
2012-10-03 | E-GEOD-34027 | biostudies-arrayexpress
Project description:Tibetan chickens, a unique plateau breed, have good performances to adapt to high-altitude hypoxic environments. A number of positively selected genes have been reported in Tibetan chickens; however, the mechanisms of gene expression for hypoxia adaptation are not fully understood. In the present study, eggs from Tibetan (TC) and Chahua (CH) chickens were incubated under hypoxic and normoxic conditions, and vascularization in the chorioallantoic membrane (CAM) of embryos was observed. We found that the vessel density index (VDI) in CAM of TCs was lower than in CHs under hypoxia incubation.Proteomic analyses of CAM tissues were performed in TC and CH embryos under hypoxic incubation using iTRAQ. We obtained 387 differentially expressed proteins (DEPs) that were mainly enriched in angiogenesis, vasculature development, blood vessel morphogenesis, blood circulation, renin-angiotensin system, and HIF-1 and VEGF signaling pathways. Twenty-six genes involved in angiogenesis and blood circulation, two genes involved in ion transport, and six genes that regulated energy metabolism were identified as candidate functional genes in regulating hypoxic adaption of chicken embryos. Therefore, this research provided insights into the molecular mechanism of hypoxia adaptation in Tibetan chickens.
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