Thrombospondin-1 in glioblastoma development
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB23786 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR2213780.fastq.gz | Fastqsanger.gz | |||
| ERR2213780_1.fastq.gz | Fastqsanger.gz | |||
| ERR2213780_2.fastq.gz | Fastqsanger.gz | |||
| ERR2213781.fastq.gz | Fastqsanger.gz | |||
| ERR2213781_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 48 |
Similar Datasets
Project description:Gliomas synaptically integrate into neural circuits. Prior work has demonstrated bidirectional interactions between neurons and glioma cells, with neuronal activity driving glioma growth and gliomas increasing neuronal excitability. In this study we sought to determine how glioma-induced neuronal changes influence neural circuits underlying cognition and whether these interactions influence patient survival. Using intracranial brain recordings during lexical retrieval language tasks in awake humans together with site-specific tumor tissue biopsies and cell biology experiments, we found that gliomas remodel functional neural circuitry such that task-relevant neural responses activate tumor-infiltrated cortex well beyond the cortical regions normally recruited in the healthy brain. Site-directed biopsies from regions within the tumor that exhibit high functional connectivity between the tumor and the rest of the brain are enriched for a glioblastoma subpopulation that exhibits a distinct synaptogenic and neuronotrophic phenotype. Tumor cells from functionally connected regions secrete the synaptogenic factor thrombospondin-1, which contributes to the differential neuron-glioma interactions observed in functionally connected tumor regions compared to tumor regions with less functional connectivity. Pharmacological inhibition of thrombospondin-1 through the FDA-approved drug, gabapentin decreases glioblastoma proliferation. The degree of functional connectivity between glioblastoma and the normal brain negatively impacts both patient survival and language task performance. These data demonstrate that high-grade gliomas functionally remodel neural circuits in the human brain, which both promotes tumor progression and impairs cognition.
2023-01-20 | GSE223065 | GEO
Project description:The gene expression profiles of two groups of triplicate human glioblastoma (GBM) xenografts grown in immunodeficient rats were compared. The first group of xenografts was derived from a patient biopsy with Epidermal Growth Factor Receptor (EGFR) amplification which grows highly invasive and is independent of angiogenesis. The second group was obtained by introducing a dominant-negative EGFR mutant into the tumor cells, leading to a progression of the tumors to an angiogenic phenotype associated with a transition from a proneural to a mesenchymal GBM molecular subtype.
2017-07-05 | E-MTAB-4898 | biostudies-arrayexpress
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
Project description:Thrombospondin 1 (TSP-1) is an anti-angiogenic matricellular protein with regulatory functions in inflammation and cancer. The type 1 repeats (TSR) domains of TSP-1 have been shown to interact with a wide range of proteins that result in the anti-angiogenic and anti-tumor properties of TSP-1. To evaluate potential therapeutic effects of TSRs in inflammatory bowel disease, we conducted clinical, histological and gene microarray analyses on a mouse model of induced colitis. We used Affymetrix GeneChips to determine the changes in the genetic profile underlying TSR-treatment coincident with induction of colitis using DSS. We identified differentially expressed genes among the treatment groups. Using DSS (dextran sulfate sodium) to induce colitis, wild-type mice were simultaneously injected with either saline or one form of TSP-1 derived peptides, containing either the three domains of the TSR (3TSR), the two last domains (TSR2), or TSR2 with the RFK sequence (TSR2+RFK). Wt mice drinking water only was used as reference.
2014-08-26 | E-GEOD-32697 | biostudies-arrayexpress
Project description:Thrombospondin 1 (TSP-1) is an anti-angiogenic matricellular protein with regulatory functions in inflammation and cancer. The type 1 repeats (TSR) domains of TSP-1 have been shown to interact with a wide range of proteins that result in the anti-angiogenic and anti-tumor properties of TSP-1. To evaluate potential therapeutic effects of TSRs in inflammatory bowel disease, we conducted clinical, histological and gene microarray analyses on a mouse model of induced colitis. We used Affymetrix GeneChips to determine the changes in the genetic profile underlying TSR-treatment coincident with induction of colitis using DSS. We identified differentially expressed genes among the treatment groups.
2014-08-26 | GSE32697 | GEO
Project description:Here, we analyzed patient-derived glioblastoma xenografts generated in the mouse brain that give rise to three different histological phenotypes: (i) a highly invasive phenotype (ii) a highly angiogenic phenotype and (iii) an intermediate phenotype. Cell type-specific transcriptomic profiles of tumor and stromal endothelial cells were analyzed to reveal phenotype-specific gene expression patterns and the reciprocal crosstalk between tumor and stromal endothelial cells. This part of the study contains the analysis of the stromal endothelial cells of the host mice. The analysis of the patient-derived tumor cells is found under E-MTAB-3948.
2016-06-30 | E-MTAB-3949 | biostudies-arrayexpress
Project description:Here, we analyzed patient-derived glioblastoma xenografts generated in the mouse brain that give rise to three different histological phenotypes: (i) a highly invasive phenotype (ii) a highly angiogenic phenotype and (iii) an intermediate phenotype. Cell type-specific transcriptomic profiles of tumor and stromal endothelial cells were analyzed to reveal phenotype-specific gene expression patterns and the reciprocal crosstalk between tumor and stromal endothelial cells. This part of the study contains the analysis of the patient-derived tumor cells. The analysis of the stromal endothelial cells of the host mice is found under E-MTAB-3949.
2016-06-30 | E-MTAB-3948 | biostudies-arrayexpress
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.
2008-11-16 | GSE13470 | GEO
Project description:Glioblastomas are brain tumors that are derived from astrocytes or oligodendrocytes. These tumors have a heterogeneous structure composed of a necrotic and vascularized center and an invasive periphery. The rapid development of glioblastoma and its ability to invade surrounding tissues makes it a complex pathology to treat, and the average survival of patients ranging from 12 to 15 months. The first and second lines of treatment, based on the Stupp protocol, consisting of the resection of the tumor mass and adjuvant temozolomide treatment and/or radiotherapy, only allow delaying recurrence for a few months. The additional use of anti-angiogenic treatment, despite its initial effects on tumor vascularization and the central tumor core, invariably leads to tumor escape. Tumor cell invasion is the central element in tumor recurrence. It is therefore important to understand the mechanisms of tumor invasion and understand the interactions between tumor cells and their microenvironment. Here, we performed proteomics analysis of glioblastoma core and invasive areas, tumor derived from a patient xenograft. Bioinformatics data analysis allowed us to identify molecules that may represent markers of tumor invasion. We established novel protein signatures such as phopholipoprotein-1 (PLP1), 2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNP) or Dynamin-1 (DNM1), and validated them in tumor samples. Finally, a functional validation was carried out in in vitro experiments. To conclude, our results report novel unexpected proteins that are involved in GBM invasion and that may constitute novel therapeutic targets.
2021-06-10 | PXD012791 | Pride
Project description:Glioblastoma cells are characterized by a highly invasive behavior whose mechanisms are not yet understood. Using the wound healing and Boyden chamber assays we compared in the present study the migration and invasion abilities of 5 glioblastoma cell lines (DK-MG, GaMG, U87-MG, U373-MG, SNB19) differing in p53 and PTEN status. We also analyzed by Western blotting the expression of PTEN, p53, mTOR and several other marker proteins involved in cell adhesion, migration and invasion. Among 5 cell lines, GaMG cells exhibited the fastest rate of wound closure, whereas U87-MG cells showed the most rapid chemotactic migration in the Boyden chamber assay. In DK-MG and GaMG cells, F-actin mainly occurred in the numerous stress fibers spanning the cytoplasm, whereas U87-MG, U373-MG and SNB19 cells preferentially expressed F-actin in filopodia and lamellipodia. Moreover, the two glioblastoma lines mutated in both p53 and PTEN genes (U373-MG and SNB19) were found to exhibit the fastest invasion rates through the Matrigel matrix. Here, we performed a gene expression profiling of the five glioblastoma cell lines to examine the molecular framework of differences in invasive behavior to find possible targets for chemo- and radiation therapy.
2014-09-05 | E-GEOD-53124 | biostudies-arrayexpress