Identification of Molecular Pathways Facilitating Glioma Cell Invasion In Situ
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Maggie Cam
PROVIDER: E-GEOD-53717 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:The aim of the experiment was to identify differences in gene expression in the whole brain hemisphere due to the presence of a brain tumor. At 21 days after a stereotactic injection of 5 x 10E4 rat C6 glioma cells into the right striatum of the rat the animals were sacrificed and the tumor-bearing brain hemispheres were isolated. The control animals were left untreated. The focus of the experiment was on the changes in gene expression due to the immune cells infiltrating the tumor and the surrounding brain parenchyma.
2017-08-31 | E-MTAB-5049 | biostudies-arrayexpress
Project description:The aim of the experiment was to identify differences in gene expression in the microglia due to the presence of a brain tumor, at 14 days after a stereotactic injection of 5 x 10E4 rat C6 glioma cells into the right striatum of the rat. The control (naive) animals were left untreated. The brain hemispheres from the control animals, or the tumor-bearing hemispheres were dissected, gently dissociated into cells and the microglia (CD11b+CD45low cells) were sorted out.
2018-01-22 | E-MTAB-5050 | biostudies-arrayexpress
Project description:Analysis of the effects of targeting NOS2 at the gene expression level. Our studies demonstrated a role for NOS2 in glioma biology through the maintenance of the glioma stem cell phenotype. Microarray results provide novel targets of NOS2 and suggest mechanisms through which NOS2 contributes to glioma stem cell biology. Glioma stem cells isolated from two different human glioma xenografts were infected with a non-targeting control shRNA or two different shRNAs directed against NOS2 (each treatment in each tumor performed in technical duplicates).
2011-07-08 | E-GEOD-29750 | biostudies-arrayexpress
Project description:Gliomas are mostly incurable secondary to their diffuse infiltrative nature. Thus, specific therapeutic targeting of invasive glioma cells is an attractive concept. As cells exit the tumor mass and infiltrate brain parenchyma, they closely interact with a changing micro-environmental landscape that sustains tumor cell invasion. In this study, we used a unique microarray profiling approach on a human glioma stem cell (GSC) xenograft model to explore gene expression changes in situ in invading glioma cells compared to tumor core, as well as changes in host cells residing within the infiltrated microenvironment relative to the unaffected cortex.
2014-02-20 | GSE53717 | GEO
Project description:Glial progenitor cells (GPCs) of the adult human white matter, which express gangliosides recognized by monoclonal antibody A2B5, are a potential source of glial tumors of the brain. We used A2B5-based sorting to extract progenitor-like cells from a range of human glial tumors, that included low-grade glioma, oligodendroglioma, oligo-astrocytomas, anaplastic astrocytoma, and glioblastoma multiforme. The A2B5+ tumor cells proved tumorigenic upon orthotopic xenograft, and the tumors generated reflected the phenotypes of those from which they derived. Expression profiling revealed that A2B5+ tumor progenitors expressed a cohort of genes by which they could be distinguished from A2B5+ GPCs isolated from normal adult white matter. Most of the genes differentially expressed by glioma-derived A2B5+ cells varied as a function of tumor stage; however, a small number were invariably expressed at all stages of gliomagenesis. These glioma progenitor-associated genes included CD24, SIX1 and EYA1, which were up-regulated at all stages of gliomagenesis, and MTUS1 and SPOCK3, which were down-regulated at all stages of tumor progression. qPCR and immunolabeling confirmed the differential expression of these genes in primary gliomas, while pathway analysis permitted their segregation into differentially active signaling pathways. By comparing the expression patterns of glial tumor progenitors to their identically-isolated normal homologues, we have identified a discrete set of oncogenic pathways by which glial tumorigenesis may be both better understood, and more efficiently targeted. Samples originating from patients with matched disease and/or pathology were considered as replicates either on the basis of exact tumor phenotype, tumor grade, or tumor vs. normal tissue samples.
2013-05-16 | E-GEOD-29796 | biostudies-arrayexpress
Project description:Glioblastoma is one of the deadliest malignancies worldwide and is virtually incurable due to its highly infiltrative growth and limited sensitivity to conventional treatment by radiochemotherapy. It is hypothesized that a small population of cells with a stem-like phenotype is the major culprit of tumor recurrence. These cells are characterized by an enhanced DNA repair capacity and expression of stemness marker genes, and elimination of this population might delay or even stop tumor recurrence following radiochemotherapy. The aim of this study was to analyze whether interference with the Hedgehog signaling (Hh) pathway or combined Hh/Notch blockade can efficiently target these cancer stem cells and sensitize them to chemotherapeutic drugs. Using tumor sphere lines and primary glioma cells we demonstrate that the Hh pathway inhibitor GANT61 (GANT) and the Hh/Notch inhibitor arsenic trioxide (ATO) are capable to synergistically decrease proliferation and induce cell death in combination with the natural cotton derived anticancer agent (-)-Gossypol (Gos). In contrast to GANT in combination with Gos, the ATO/Gos combination also strongly prevented sphere formation and recovery. These synergistic effects were associated with major proteomic changes indicating decreased cell movement, distortion of cell cycle and DNA repair, as well as markedly reduced stemness. Collectively, our data show that ATO and Gos, two drugs that are safe for use in humans, represent a promising targeted therapy approach for the synergistic and specific elimination of glioma stem-like cells.
2019-03-13 | PXD009249 | Pride
Project description:Comparison of polysomal profiles of murine adult olig2 cortical progenitors, murine tumor olig2 cells derived from hPDGF-B-driven glioblastomas, and murine olig2 proliferative recruited glioma cells contributing to the tumor mass but not derived from the cell of origin An unbiased way to define a cell population lies in identification of its gene expression signature and subsequent comparison to gene expression signatures of known normal or cancer cells to define its position on the axis of tumorigenesis. To quantify similarities and differences in the expression profiles of recruited cells and tumor cells using microarray analysis, we used the bacTRAP technology that allows immunoprecipitation of polysomes from specific cell types in vivo (Heiman et al 2008, Doyle et al 2008). We compared polysomal expression profiles of hPDGFb-driven Ntv-a Ink4a/Arf+/- olig2 mouse glioma cells representing a histologically defined glioma population, recruited olig2 cells derived from Ink4a/Arf+/- olig2 RP-eGFP mice transplanted with non-fluorescent glioma cells, and normal adult cortical olig2 mouse progenitors, using Affymetrix 430 mouse 2.0 chips and Genespring GX10 software (Doyle et al 2008, Heiman et al 2008). Translational profiles of recruited olig2 cells and glioma olig2 cells were similar to each other and clearly distinct from the normal olig2 progenitors, majority of the differences accounted for by the “statistically significantly changed” set of mRNAs (ANOVA, p<0.05), and sample clustering reduced upon removal of the ANOVA-tested mRNA set. Unsupervised hierarchical mRNA clustering likewise indicated that recruited olig2 cells clustered more closely to glioma olig2 cells. The caveat is that olig2 expression in the adult normal brain of bacTRAP olig2 RP-eGFP mice labels both progenitors and mature oligodendrocytes, while recruited and tumor olig2 cells are almost entirely progenitors; therefore, some of the differences seen in the comparative analysis of normal, tumor and recruited olig2 cells may in part result from the shift in relative abundance of different progenitor and mature olig2 cell populations. Normal olig2 progenitors were collected from three replicates of pooled cortices of three olig2 RP-eGFP bacTRAP reporter mice. Mouse gliomas induced by injection of a non-fluorescent RCAS-hPDGFb (Shih et al 2004) or by transplantation of muring glioma cells derived from Ntv-a gliomas induced by the non-fluorescent RCAS-hPDGFb were collected from Ntv-a olig2 RP-eGFP bacTRAP reporter mice and immunoprecipitated; each tumor was processed as a separate sample. Briefly, mouse tissues were collected into ice-cold cyclohexamide-containing buffer, homogenized, cells were lysed in NP-40 and DHPC-containing buffer, centrifuged at 20,000g for 15 min, supernatant incubated with anti-eGFP-conjugated protein G beads 30 min at 4C, washed and RNA collected using Trizol reagent as per manufacturer’s instructions (Doyle et al., 2008; Heiman et al., 2008). RNA was purified, concentrated using Qiagen RNeasy kit, its quality confirmed by Agilent Bioanalyzer, 15ng per sample amplified using Affymetrix Two-Cycle Amplification kit and hybridized to Affymetrix 430 mouse 2.0 chips as described in Doyle et al., 2008; Heiman et al., 2008. Data was analyzed using Genespring GX10 software, as described in the text and in Doyle et al., 2008; Heiman et al., 2008. Briefly, samples were normalized using GCRMA, filtered to remove probe sets with low intensity, and analyzed using ANOVA (p<0.05) with SNK post-hoc and Benjamini and Hochberg FDR multiple testing correction. Probe quality, Pearson’s correlation, hierarchical clustering, heatmaps, gene profile plots were generated using Genespring GX10 software. Pathway analysis was performed using Ingenuity as per manufacturer’s instructions. Gliomas are thought to form by clonal expansion from a single cell-of-origin, and progression-associated mutations to occur in its progeny cells. Glioma progression is associated with elevated growth factor signaling and loss of function of tumor suppressors Ink4a, Arf and Pten. Yet, gliomas are cellularly heterogeneous; they recruit and trap normal cells during infiltration. We performed lineage tracing in a retrovirally mediated, molecularly and histologically accurate mouse model of hPDGFb-driven gliomagenesis. We were able to distinguish cells in the tumor that were derived from the cell-of-origin from those that were not. Phenotypic, tumorogenic and expression analyses were performed on both populations of these cells. Here we show that during progression of hPDGFb-induced murine gliomas, tumor suppressor loss can expand the recruited cell population not derived from the cell-of-origin within glioma microenvironment to dominate regions of the tumor, with essentially no contribution from the progeny of glioma cell-of-origin. Moreover, the recruited cells can give rise to gliomas upon transplantation and passaging, acquire polysomal expression profiles and genetic aberrations typically present in glioma cells rather than normal progenitors, aid progeny cells in glioma initiation upon transplantation, and become independent of PDGFR signaling. These results indicate that non-cell-of-origin derived cells within glioma environment in the mouse can be corrupted to become bona fide tumor, and deviate from the generally established view of gliomagenesis.
2011-06-17 | E-GEOD-30016 | biostudies-arrayexpress
Project description:MicroRNAs (miRNAs) are non-coding molecules involved in post-transcriptional gene regulation that have been shown to modulate tumor cell proliferation and apoptosis and to act as oncogenes or tumor-suppressor genes. Although miRNAs have been linked to tumor progression, the connection between tumor-mediated immune modulation and miRNAs has yet to be explored. Specifically, how the miRNA dysregulation affects the monocyte-derived glioblastoma-infiltrating macrophages, the most abundant immune cell population within the glioblastoma microenvironment, and their immune suppressive properties has not been evaluated to date. Here we managed to purify the glioblastoma-infiltrating macrophages from the tumor microenvironment and compared their miRNA expression profile with the matched peripheral monocytes from the peripheral blood of the same GBM patient as well as with healthy donors. Of note, several most down-regulated miRNA candidates revealed in this study, including miR-142-3p, were also known for their role in mediating tumor-associated immunosuppression. These results suggest a novel approach to identify miRNA immune therapeutics using a two-step process: 1) screen miRNA expression from tumor-associated immune cells relative to normal immune cell, and 2) select and prioritize potential candidates on the basis of binding to immunosuppressive pathways or mechanisms. In the study presented here, 12 samples, including peripheral monocyte samples from 4 healthy donors, peripheral monocytes from 4 GBM patients and matched tumor-infiltrating macrophages extracted from the glioblastoma microenvironment, were used to acquire the miRNA expression profiles of 1732 unique mature miRNA sequences via the Phalanx Human miRNA OneArray Microarray v3 Platform.
2014-09-23 | E-GEOD-51332 | biostudies-arrayexpress
Project description:Microglia isolated from glioma patients gain anti-tumor activities upon poly (I:C) stimulation. Expression profiles of human tumor-infiltrating microglia/macrophages before (untreated) and after treatment with poly (I:C) for 48h (induced). Tumor-infiltrating microglia/macrophages were isolated from freshly excised brain tumors
2011-12-31 | E-GEOD-25289 | biostudies-arrayexpress
Project description:Many subsets of myeloid cells have been identified over the years, some of which are extremely rare populations. Previously, we identified the optimal protocol for proteomics studies in paucicellular myeloid samples [PXD018872], which was implemented here to investigate cellular relationships of small myeloid cell populations from peripheral blood and glioma material.
2023-02-09 | PXD026604 | Pride