Pp71-stimulated genes in U87 stable cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE42618 | GEO | 2017/02/09
SECONDARY ACCESSION(S): PRJNA182364
REPOSITORIES: GEO
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Project description:Glioblastoma multiforme (GBM), is the most malignant and common tumor among glial neoplasms. It is characterized by a peak of incidence between 45 and 70 years and a patient median survival time of 14.6 months. In addition, GBM undergoes malignant progression under hypoxic conditions that contributes to strong radioresistance and chemoresistance; alters the metabolism of the tumor cells; generates a strong genome instability, increases the angiogenesis, vasculogenesis, and contributes to the formation of the Cancer Stem Cells (CSCs) and the infamous Circulating Tumor Cells (CTCs) involved in metastasis formation. Moreover, GBMs have a poor prognosis due to treatment (such as surgical resection, conventional RT and chemotherapy) plan failures. In this sense, since standard GBM treatments are not effective, new promising strategies such as Proton Therapy (PT), are under investigation because supported by encouraging results. Considering these assumptions, the main aim of this study was to analyze GBM response to PT innovative treatment during induced acute hypoxia, by using a whole gene expression analysis. Thus, in this work we have reported in a descriptive way, the most statistically and biologically relevant pathways deregulated in U87 GBM cell line, according to specific PT plans during hypoxia condition, and in addition, some interesting biomarker networks were following discussed.
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2013-12-02 | E-GEOD-43674 | biostudies-arrayexpress
Project description:Glioblastoma multiforme (GBM) brain tumours have one of the shortest mean survival times (<1 year). In vivo models of GBM in mice and rats have been developed to study aspects of glioma that cannot be observed in cell culture such as angiogenesis, invasion and metastasis. Gliomas can be induced by implantation of rodent glioma cell lines into the brain or flank of nude mice. The disadvantages of rodent models however include variable growth rate and poor penetrance, which leads to difficulties in collecting clearly graded samples (pre-vascular/vascular). Bikfalvi et al have previously established a human GBM model that addresses these issues based on the chicken egg chorio-allantoic membrane (CAM), a highly vascularised extra-embryonic tissue. We have used DNA microarrays and a CAM model of GBM to study gene expression during the recruitment and development of the tumour vasculature. Over a 5 day period samples were taken every 12 hours from the tumour implantation site consisting of tumour cells and stroma cells, and also from a site distant from the implantation site consisting of just CAM cells. This study will shed light on the dynamic transcriptional signature of pathological angiogenesis.
2013-12-02 | GSE43674 | GEO
Project description:Glioblastoma (GBM) remains a challenging malignancy with dismal prognoses despite aggressive treatment regimens. Intratumoral heterogeneity contributes to therapeutic resistance, with roles for stem cell-like brain tumor initiating cells (GBMs), glioma associated macrophages (GAMs), and communication between them. GAMs are derived from infiltrating lymphocytes, and monocyte migration is increased by GBM cell release of extracellular vesicles, including exosomes. GBM survival is promoted by the glucose transporter GLUT3, which was recently shown to alter macrophage activation states. We found that GBM-derived exosomes contain GLUT3 and that exosomes from GLUT3 expressing GBMs significantly increased monocyte migration in comparison to controls. Monocytes transfected with GLUT3 (but not GLUT1) also had significantly increased migration, demonstrating a direct role for GLUT3 in monocytes migration. Analysis of the transcriptome of exosome treated monocytes demonstrated that exosomes derived from GLUT3 expressing GBMs increasedGDF-15in monocytes. GDF-15 is a known regulator of monocyte migration, and we determined that knockdown of GDF-15 blocked the migration induced by GBM-derived exosomes. As GDF-15 induced monocyte migration is thought to involve MMP12, we next evaluated MMP12 as a potential mediator of the pro-migratory phenotype.MMP12was significantly increased in monocytes upon treatment with exosomes derived from GLUT3 expressing GBMs as was MMP12 activity. Together, our findings suggest a novel mechanism by which GBMs facilitate immune evasion and tumor progression: GBM-derived exosomes transfer GLUT3 to monocytes to increase a GDF-15/MMP12 pathway that promotes monocyte migration. The data also highlight the importance of understanding and targeting cell-cell interactions to improve glioblastoma treatment.
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Project description:Glioblastoma multiforme (GBM) is the most common form of malignant glioma and is characterized by marked genetic instability, extensive intra-tumoral histopathological variability, and unpredictable variation in its clinical behavior. We investigated global gene expression in surgical samples of primary brain tumors. Gene expression profiling revealed large differences between normal brain samples and tumor tissues and between GBMs and lower grade oligodendroglial tumors. Extensive differences in gene expression were found among GBMs, particularly in genes involved in angiogenesis, immune cell infiltration, and extracellular matrix re-modeling. Significantly, we found that the global gene expression patterns in paired specimens from the same GBM invariably were more closely related to each other than to any other tumor, even when the paired specimens had strikingly divergent histologies. Survival analyses revealed a set of approximately 70 genes that were more highly expressed in rapidly progressing tumors and which stratified GBMs into two groups that differed by more than four-fold in median duration of survival. We further investigated one gene from the group, FABP7, and confirmed its association with survival in two unrelated cohorts totaling 105 patients. Expression of FABP7 enhanced the motility of glioma-derived cells in vitro. Our analyses thus provide a series of prognostic markers and suggest that their expression may enhance the invasive potential of tumor cells.
2005-11-11 | E-SMDB-2677 | biostudies-arrayexpress
Project description:<h4><strong>BACKGROUND:</strong> Elevated choline kinase alpha (ChoK) is observed in most solid tumours including glioblastomas (GBM), yet until recently, inhibitors of ChoK have demonstrated limited efficacy in GBM models. Given that hypoxia is associated with GBM therapy resistance, we hypothesised that tumour hypoxia could be responsible for such limitations. We therefore evaluated in GBM cells, the effect of hypoxia on the function of JAS239, a potent ChoK inhibitor.</h4><h4><strong>METHODS:</strong> Rodent (F98 and 9L) and human (U-87 MG and U-251 MG) GBM cell lines were subjected to 72 hours of hypoxia conditioning and treated with JAS239 for 24 hours. NMR metabolomic measurements and analyses were performed to evaluate the signalling pathways involved. In addition, cell proliferation, cell cycle progression and cell invasion were measured in cell monolayers and 3D spheroids, with or without JAS239 treatment in normoxic or hypoxic cells to assess how hypoxia affects JAS239 function.</h4><h4><strong>RESULTS:</strong> Hypoxia and JAS239 treatment led to significant changes in the cellular metabolic pathways, specifically the phospholipid and glycolytic pathways associated with a reduction in cell proliferation via induced cell cycle arrest. Interestingly, JAS239 also impaired GBM invasion. However, JAS239 effects were variable depending on the cell line, reflecting the inherent heterogeneity observed in GBMs.</h4><h4><strong>CONCLUSION:</strong> Our findings indicate that JAS239 and hypoxia can deregulate cellular metabolism, inhibit proliferation and alter cell invasion. These results may be useful for the design of new therapeutic strategies based on ChoK inhibition that can act on multiple pro-tumorigenic features.</h4>
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Project description:Glioblastoma multiforme (GBM) is the most common form of malignant glioma and is characterized by marked genetic instability, extensive intra-tumoral histopathological variability, and unpredictable variation in its clinical behavior. We investigated global gene expression in surgical samples of primary brain tumors. Gene expression profiling revealed large differences between normal brain samples and tumor tissues and between GBMs and lower grade oligodendroglial tumors. Extensive differences in gene expression were found among GBMs, particularly in genes involved in angiogenesis, immune cell infiltration, and extracellular matrix re-modeling. Significantly, we found that the global gene expression patterns in paired specimens from the same GBM invariably were more closely related to each other than to any other tumor, even when the paired specimens had strikingly divergent histologies. Survival analyses revealed a set of approximately 70 genes that were more highly expressed in rapidly progressing tumors and which stratified GBMs into two groups that differed by more than four-fold in median duration of survival. We further investigated one gene from the group, FABP7, and confirmed its association with survival in two unrelated cohorts totaling 105 patients. Expression of FABP7 enhanced the motility of glioma-derived cells in vitro. Our analyses thus provide a series of prognostic markers and suggest that their expression may enhance the invasive potential of tumor cells. A disease state experiment design type is where the state of some disease such as infection, pathology, syndrome, etc is studied. Using regression correlation
2006-01-18 | E-GEOD-4058 | biostudies-arrayexpress
Project description:Frequent discrepancies between preclinical and clinical results of anti-cancer agents demand a reliable translational platform that can precisely recapitulate the biology of human cancers. Another critical unmet need is the ability to predict therapeutic responses for individual patients. Toward this goal, we have established a library of orthotopic glioblastoma (GBM) xenograft models using surgical samples of GBM patients. These patient-specific GBM xenograft tumors recapitulate histopathological properties and maintain genomic characteristics of parental GBMs in situ. Furthermore, in vivo irradiation, chemotherapy, and targeted therapy of these xenograft tumors mimic the treatment response of parental GBMs. We also found that establishment of orthotopic xenograft models portends poor prognosis of GBM patients and identified the gene signatures and pathways signatures associated with the clinical aggressiveness of GBMs. Together, the patient-specific orthotopic GBM xenograft library represent the preclinically and clinically valuable “patient tumor’s phenocopy” that represents molecular and functional heterogeneity of GBMs. aCGH experiments were performed for a human glioblastoma tissue (sample ID: PC-NS08-559) and the matching xenograft tumor tissue using the Agilent Human Whole Genome CGH 244K microarray according to manufacturer's protocol (2-color).
2013-01-18 | E-GEOD-42577 | biostudies-arrayexpress