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Established glioma cell lines prove valuable models for tumour heterogeneity - mediated cellular response studies in vitro

ABSTRACT: Both established glioma cells lines U87MG and U373 were used for studying their interactions in the indirect co-cultures. Eventhough both being derived from the glioma tissue, those two cell lines prove morphologically and physiologically disctinct. Therefore their intre-cellular interactions were examined on gene exprexssion level in vitro to observe whether those co-cultures could make for a suitable in vitro cell model mimicking the in vivo glioma tumour heterogeneity.

ORGANISM(S): Homo sapiens

PROVIDER: GSE59634 | GEO | 2015/04/08

SECONDARY ACCESSION(S): PRJNA255790

REPOSITORIES: GEO

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Established glioma cell lines prove valuable models for tumour heterogeneity - mediated cellular response studies in vitro

Project description:Both established glioma cells lines U87MG and U373 were used for studying their interactions in the indirect co-cultures. Eventhough both being derived from the glioma tissue, those two cell lines prove morphologically and physiologically disctinct. Therefore their intre-cellular interactions were examined on gene exprexssion level in vitro to observe whether those co-cultures could make for a suitable in vitro cell model mimicking the in vivo glioma tumour heterogeneity. Three biological replicates of four cell set-ups were performed: U87MG monoculture, U373 monoculture, U87MG co-cultured with U373 (in Boyden chambers) and U373 co-cultured with U87MG (in Boyden chambers).

2015-04-08 | E-GEOD-59634 | biostudies-arrayexpress

Frizzled 4 regulates stemness and invasiveness of migrating glioma cells established by serial in vivo intracranial transplantation

Project description:One of the most detrimental hallmarks of glioblastoma multiforme (GBM) is cellular invasiveness, considered a potential cause of tumor recurrence. Infiltrated GBM cells are difficult to completely eradicate surgically and with local therapeutic modalities. Although much effort has focused on understanding the various mechanisms controlling GBM invasiveness, the nature of the invasiveness remains poorly characterized. Here, we established a highly invasive glioma cell line (U87R4 cells) and a non-invasive cell line (U87L4 cells) from U87MG glioma cells following four rounds of serial in vivo intracranial transplantation. Compared to U87L4 cells, U87R4 cells were highly invasive and had glioma stem cell-like properties. Microarray analysis showed that apoptosis-inducing genes (caspase3 and PDCD4) were downregulated, whereas several cancer stem cell-relevant genes (Wnt10A, Frizzled 4, and CD44) were upregulated in U87R4 cells compared to U87L4 cells. U87R4 cells were resistant to anticancer drug-induced cell death, which was partially due to downregulation of caspase3 and PDCD4. U87R4 cells retained activated Wnt/Î²-catenin signaling through Frizzled 4, which was sufficient to control neurosphere formation. In addition, Frizzled 4 promoted expression of the epithelial to mesenchymal transition regulator, SNAI1, and acquisition of a mesenchymal phenotype. Taken together, our results indicate that Frizzled 4 may be a member of the Wnt signaling family that governs both stemness and invasiveness of glioma stem cells, and may be a major cause of GBM recurrence and poor prognosis. We established a highly invasive glioma cell line (U87R4 cells) and a non-invasive cell line (U87L4 cells) from U87MG glioma cells following four rounds of serial in vivo intracranial transplantation to characterize the mRNA expression profile of highly invasive glioma cells compared to non-invasive/parental glioma cell lines.

2010-05-27 | E-GEOD-21570 | biostudies-arrayexpress

Differential gene expression analysis of U87MG EGFRvA cells vs. U87MG EGFR cells

Project description:EGFRvA is a novel and widely-expressed EGFR isoform, whose upregulation is positively related to glioma grades. Intriguingly, it is the upregulation of EGFRvA but not EGFR that significantly correlates with a poor prognosis in glioma patients. Cancer cells expressing EGFRvA (relative to EGFR) display a higher invasive capacity and a lower sensitivity to EGFR tyrosine kinase inhibitors (TKIs). To investigate the significant differently expressed genes between U87MG EGFRvA cells and U87MG EGFR cells，microarray experiments were conducted.

2012-09-30 | GSE41230 | GEO

Differential gene expression analysis of U87MG EGFRvA cells vs. U87MG EGFR cells

2012-09-30 | E-GEOD-41230 | biostudies-arrayexpress

Frizzled 4 regulates stemness and invasiveness of migrating glioma cells established by serial in vivo intracranial transplantation

Project description:One of the most detrimental hallmarks of glioblastoma multiforme (GBM) is cellular invasiveness, considered a potential cause of tumor recurrence. Infiltrated GBM cells are difficult to completely eradicate surgically and with local therapeutic modalities. Although much effort has focused on understanding the various mechanisms controlling GBM invasiveness, the nature of the invasiveness remains poorly characterized. Here, we established a highly invasive glioma cell line (U87MGR2/R3 cells) and a non-invasive cell line (U87MGL2/L3 cells) from U87MG glioma cells following four rounds of serial in vivo intracranial transplantation. Compared to U87MGL2/L3 cells, U87MGR2/R3 cells were highly invasive and had glioma stem cell-like properties. Microarray analysis showed that apoptosis-inducing genes (caspase3 and PDCD4) were downregulated, whereas several cancer stem cell-relevant genes (Wnt10A, Frizzled 4, and CD44) were upregulated in U87MGR2/R3 cells compared to U87MGL2/L3 cells. U87MGR2/R3 cells were resistant to anticancer drug-induced cell death, which was partially due to downregulation of caspase3 and PDCD4. U87MGR2/R3 cells retained activated Wnt/β-catenin signaling through Frizzled 4, which was sufficient to control neurosphere formation. In addition, Frizzled 4 promoted expression of the epithelial to mesenchymal transition regulator, SNAI1, and acquisition of a mesenchymal phenotype. Taken together, our results indicate that Frizzled 4 may be a member of the Wnt signaling family that governs both stemness and invasiveness of glioma stem cells, and may be a major cause of GBM recurrence and poor prognosis.

2010-04-29 | GSE21570 | GEO

Inhibition of Mitochondria NADH–Ubiquinone Oxidoreductase (Complex I) Sensitizes the Radioresistant Glioma Cells to Radiation

Project description:We cumulatively radiated a glioblastoma cell line, U87MG, and screened radioresistant glioma cells. A transcriptome sequencing was performed to analyze the transcription differences between the raidoresistant and control cells.

2020-01-15 | GSE143609 | GEO

Functional expression of membrane alanyl-aminopeptidase (CD13/APN) promotes tumor cell proliferation and neoangiogenesis in malignant gliomas.

Project description:Malignant gliomas are characterized by marked neovascularization and increased tumor cell proliferation. Recently, membrane alanyl-aminopeptidase (CD13/APN) has been identified to play a crucial role in neoangiogenesis. In this study, we show that among various central nervous system tumors, malignant astrocytomas are unique in their high expression levels of functionally active CD13/APN. CD13/APN was found in both tumor cells and tumor vessels of malignant astrocytomas, while in low-grade astrocytomas only endothelial cells of tumor vessels expressed CD13/APN. Inhibitors of the enzymatic activity of CD13/APN significantly reduced the proliferation of U87MG and U138MG malignant glioma cells. Inhibition of CD13/APN mRNA expression by siRNA in glioma cells co-cultured with human umbilical vein endothelial cells (HUVEC) effectively decreased blood vessel formation. Pro-angiogenic factors like bFGF and VEGF induced CD13/APN expression in glioma cells. Treatment of U87MG and U138MG cells with CD13/APN inhibitors resulted in an increased mRNA expression of VEGF and VEGF receptor 2 (VEGF-R2) in these cells. Taken together, these findings provide evidence that CD13/APN promotes tumor cell proliferation and blood vessel formation in malignant astrocytomas. Remarkably, inhibition of CD13/APN induces an angiogenic expression profile via an autocrine feed-back mechanism involving the VEGF/VEGF-R2 system in malignant gliomas. Experimental design includes altogether four samples with two replicate controls (U87_APN_wt_EGFP) and two replicate samples (U87_APN_L243P_EGFP). Replicates are from two independent experiments.

2012-05-27 | E-GEOD-37923 | biostudies-arrayexpress

Human Mesenchymal Stem Cells Exploit the Immune Response Mediating Chemokines to Impact the Phenotype of Glioblastoma

Project description:Four human mesenchymal stem cells (hMSC) clones (MSC-1, MSC-2, MSC-3, MSC-4) and three different glioblastoma multiformae (GBM) cell lines (U87-MG, U251, U373) were used to study their mutual paracrine interactions in the indirect co-cultures compared to their monocultures, which were grown under the same experimental conditions. The effects on cell growth, proliferation and invasion in matrigel were quantified. Further on, bioinformatic tools were used to relate these results to the data obtained from cytokine macroarrays and DNA microarrays that revealed proteins and genes significantly involved in the interaction. We showed that hMSC are responsible for the impairment of GBM cell invasion and growth, possibly via induction of their senescence. On the other hand, U87-MG cells even more strongly inversely affected some of these characteristics in hMSCs. We found several chemokines that may account for changed co-cultured cells’ phenotype, affecting genes associated with proliferation and senescence. CCL2/MCP-1 was collectively identified as the most significantly regulated chemokine during hMSC and U87-MG paracrine signalling. Its role in U87-MG cell invasion was also functionally confirmed. Microarray data deposited here contain gene expression data from three biological replicates of monocultures and indirect co-cultures of MSC-4 and U87-MG cells, representing 12 microarrays.

2011-12-20 | GSE26283 | GEO

Gene expression analysis of the human glioma cell line U87MG

Project description:Identification of genes and pathways regulated by kynurenine in human glioma cells Total RNA from U87MG cells was extraced after 8h or 24h of treatment with 100µM kynurenine and compared to untreated control.

2010-11-11 | E-GEOD-25272 | biostudies-arrayexpress

Functional expression of membrane alanyl-aminopeptidase (CD13/APN) promotes tumor cell proliferation and neoangiogenesis in malignant gliomas.

2012-05-28 | GSE37923 | GEO

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