Identification of Molecular Pathways Facilitating Glioma Cell Invasion In Situ
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ABSTRACT:
PROVIDER: PRJNA232712 | ENA |
REPOSITORIES: ENA
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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. Replicate sets of mice (n=4) were inoculated with either of two different GSC's derived from from human glioma, and each mouse had samples taken from the tumor mass, the infiltrating area and the mouse brain parenchyma, resulting in 3 samples per animal. The tumor mass and infiltrating samples were hybridized on human U133Plus2 Arrays, whereas the infiltrating samples and mouse brain parenchyma were hybridized on mouse
2014-02-20 | E-GEOD-53717 | 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: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 (IGCs) compared to tumor core, as well as changes in host cells residing within the infiltrated microenvironment relative to the unaffected cortex. IGCs were found to have reduced expression of genes within the extracellular matrix compartment, and genes involved in cell adhesion, cell polarity and epithelial to mesenchymal transition (EMT) processes. The infiltrated microenvironment showed activation of wound repair and tissue remodeling networks. We confirmed by protein analysis the downregulation of EMT and polarity related genes such as CD44 and PARD3 in IGCs, and EFNB3, a tissue-remodeling agent enriched at the infiltrated microenvironment. OLIG2, a proliferation regulator and glioma progenitor cell marker upregulated in IGCs was found to function in enhancing migration and stemness of GSCs. Overall, our results unveiled a more comprehensive picture of the complex and dynamic cell autonomous and tumor-host interactive pathways of glioma invasion than has been previously demonstrated. This suggests targeting of multiple pathways at the junction of invading tumor and microenvironment as a viable option for glioma therapy.
| S-EPMC4218815 | biostudies-literature
Project description:Glioma is characterized by high migration and invasion, and the relative molecular mechanism is still poor. Accumulating studies demonstrated that ubiquitin specific protease 39 (USP39) played an oncogenic role in several cancers. Here, we investigate USP39 expression and function in human glioma. Oncomine database analysis revealed high USP39 expression in glioma and elevated USP39 expression correlated significantly with poor overall survival. Knockdown of USP39 significantly inhibited the migration and invasion of U251 and U87 cells. The gene expression profile was executed to screen the target molecules of USP39. The result showed that ADAM9, a molecule involved in migration and invasion of various human tumors, was significantly downregulated in the U251 and U87 cells with shRNA-mediated USP39 knockdown. Mechanistically, USP39 directly interacted with the ADAM9 mRNA and induced ADAM9 mRNA maturation, following the decreased expression of integrin β1. Besides, overexpressed ADAM9 rescued the inhibited migration and invasion of glioma cells causing by USP39 depletion. USP39 promoted invasion in vivo and reduced the overall survival of the mice. Collectively, USP39 may have oncogenic role that increase ADAM9 protein levels by inducing maturation of ADAM9 mRNA in glioma. USP39 could be considered a new potential therapeutic target for glioma.
2020-10-23 | GSE159823 | GEO
Project description:High-grade glioma is highly aggressive and malignant, resistant to combined therapies and easy to relapse. A better understanding of circRNA biological function in high-grade glioma might contribute to the therapeutic efficacy. Here, a circRNA merely up-regulated in high-grade glioma, circGLIS3 (hsa_circ_0002874, originating from exon 2 of GLIS3), was validated by microarray and qRT-PCR. Functional experiments uncovered that up-regulation of circGLIS3 promoted glioma cell migration and invasion, and showed aggressive characteristics in tumor-bearing mice. Fluorescence in situ hybridization, RNA pull-down, RNA immunoprecipitation and immunohistochemical staining showed that circGLIS3 could promoted Ezrin T567 phosphorylation. Further investigation showed that circGLIS3 could be excreted by glioma through exosomes and induced endothelial cells angiogenesis. This study indicates that circGLIS3 is up-regulated in high-grade glioma and contributes to the invasion and angiogenesis of glioma via promoting Ezrin T567 phosphorylation.
2021-09-22 | GSE165859 | GEO
Project description:High-grade glioma is highly aggressive and malignant, resistant to combined therapies and easy to relapse. A better understanding of circRNA biological function in high-grade glioma might contribute to the therapeutic efficacy. Here, a circRNA merely up-regulated in high-grade glioma, circGLIS3 (hsa_circ_0002874, originating from exon 2 of GLIS3), was validated by microarray and qRT-PCR. Functional experiments uncovered that up-regulation of circGLIS3 promoted glioma cell migration and invasion, and showed aggressive characteristics in tumor-bearing mice. Fluorescence in situ hybridization, RNA pull-down, RNA immunoprecipitation and immunohistochemical staining showed that circGLIS3 could promoted Ezrin T567 phosphorylation. Further investigation showed that circGLIS3 could be excreted by glioma through exosomes and induced endothelial cells angiogenesis. This study indicates that circGLIS3 is up-regulated in high-grade glioma and contributes to the invasion and angiogenesis of glioma via promoting Ezrin T567 phosphorylation.
2021-09-22 | GSE165926 | GEO
Project description:Ubiquitin-specific peptidase 39 promotes human glioma cells migration and invasion by facilitating ADAM9 mRNA maturation
| PRJNA670655 | ENA
Project description:The lateral ventricle subventricular zone (SVZ) is a frequent and consequential site of pediatric and adult glioma spread, but the cellular and molecular mechanisms mediating this are poorly understood. We demonstrate that neural precursor cell (NPC):glioma cell communication underpins this propensity of glioma to colonize the SVZ through secretion of chemoattractant signals toward which glioma cells home. Biochemical, proteomic, and functional analyses of SVZ NPC-secreted factors revealed the neurite outgrowth-promoting factor pleiotrophin, along with required binding partners SPARC/SPARCL1 and HSP90B, as key mediators of this chemoattractant effect. Pleiotrophin expression is strongly enriched in the SVZ, and pleiotrophin knockdown starkly reduced glioma invasion of the SVZ in the murine brain. Pleiotrophin, in complex with the binding partners and signaling through the receptor PTPRZ1, activated glioma Rho/ROCK signaling, and ROCK inhibition decreased invasion toward SVZ NPC-secreted factors. These findings demonstrate a pathogenic role for NPC:glioma interactions and potential therapeutic targets to limit glioma invasion.
2017-07-26 | GSE99812 | GEO
Project description:Glioblastoma multiforme (GBM) is the most prevalent and deadliest adult brain tumor. To systematically characterize the pathways governing brain invasion, we developed a three-dimensional (3D) ex vivo organotypic invasion model with clinical relevance to GBM. We used this model to enrich for highly invasive GBM cell population. Using next-generation sequencing to transcriptomically profile highly invasive and poorly invasive GBM cell populations, we have identified a network of extracellular matrix (ECM) components, including multiple collagens and collagen-interacting proteins, which are upregulated by invading GBM cells and strongly correlate in expression with clinical glioma progression outcomes. We identify the interferon regulatory factor 3 (IRF3) as a direct transcriptional repressor of ECM factors in GBM and show that IRF3 acts as an endogenous suppressor of GBM invasion. Therapeutic activation of IRF3 by inhibiting casein kinase 2 (CK2) -- a negative regulator of IRF3 phosphorylation -- downregulated the expression of ECM factors and suppressed GBM invasion in ex vivo and in vivo models across a panel of patient-derived GBM cell lines representative of the main molecular GBM subtypes in the clinic. Our findings illustrate an integrated and systematic approach for the discovery of novel pathways regulating brain tumor invasion and provide a strong mechanistic insight into the notorious, yet poorly understood, invasion capacity of GBM tumors.
2017-10-01 | GSE87535 | GEO
Project description:Preliminary research shows that,The P68 protein was highly expressed in the glioma tissue specimen and was associated with the patient's survival.Inhibition of P68 protein expression in glioma cell lines inhibits the growth, invasion and appreciation of tumor cells.In this study, gene chip was used to search for new downstream genes DUSP5 that affect the growth of glioma.The expression of inhibition or overexpression of P68 protein in glioma cell lines was consistent with the expression of expression DUSP5 and the effect of reduction DUSP5 on the growth of the tumor.The ability of the tumor to recover after the expression of DUSP5 expression in glioma cells was reduced,This indicates that P68 regulates the growth, increment and invasion of glioma cells.Through affymetrix gene chip, we use 3 biological specimens.That is three SIP68 , control of the glioma cells that infect NC.Try to get P68 protein regulated downstream gene by knocking down P68 protein.
2017-09-20 | GSE103981 | GEO