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PROVIDER: PRJNA253928 | ENA |
REPOSITORIES: ENA
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Project description:Aberrant differentiation of glioma stem cells: Implications for therapeutic targeting (shift)
| PRJNA253927 | ENA
Project description:Aberrant differentiation of glioma stem cells: Implications for therapeutic targeting [Xenograph]
| PRJNA253929 | ENA
Project description:SUMMARY Terminal differentiation has been proposed as a therapeutic strategy for glioblastoma (GBM). Culturing of GBM derived tumor initiating glioma stem cells (GSCs) in fetal bovine serum containing media is a proposed mode of differentiation that is thought to induce loss of stem cell characteristics, promote neural lineage differentiation and a parallel loss of tumor initiation capacity. Here we show that GSCs retained both neurosphere formation and tumor initiation abilities after short or long term serum exposure. Under serum induced differentiating conditions, GSCs expressed both neural lineage and stem cell markers, highlighting the aberrant pseudo-differentiation state. GSCs maintained under adherent differentiating conditions continued to proliferate and initiate tumor formation with efficiencies similar to GSCs maintained under proliferating (neurosphere) conditions. Proneural (PN) GSCs under serum exposure showed an induction of mesenchymal (MES) gene expression signatures. Our data indicate that the tumor initiation ability of GSCs is independent of their differentiation state and that terminal differentiation as a therapeutic approach may not effectively negate tumorigenicity of GSCs. SIGNIFICANCE Terminal differentiation has been proposed as a therapeutic strategy for glioblastoma (GBM). Culturing of GBM derived tumor initiating glioma stem cells (GSCs) in fetal bovine serum containing media is a proposed mode of differentiation that is thought to induce loss of stem cell characteristics, promote neural lineage differentiation and a parallel loss of tumor initiation capacity. Here we show that GSCs retained both neurosphere formation and tumor initiation abilities after short or long term serum exposure. Under serum induced differentiating conditions, GSCs expressed both neural lineage and stem cell markers, highlighting the aberrant pseudo-differentiation state. GSCs maintained under adherent differentiating conditions continued to proliferate and initiate tumor formation with efficiencies similar to GSCs maintained under proliferating (neurosphere) conditions. Proneural (PN) GSCs under serum exposure showed an induction of mesenchymal (MES) gene expression signatures. Our data indicate that the tumor initiation ability of GSCs is independent of their differentiation state and that terminal differentiation as a therapeutic approach may not effectively negate tumorigenicity of GSCs.
2015-09-01 | GSE58922 | GEO
Project description:SUMMARY Terminal differentiation has been proposed as a therapeutic strategy for glioblastoma (GBM). Culturing of GBM derived tumor initiating glioma stem cells (GSCs) in fetal bovine serum containing media is a proposed mode of differentiation that is thought to induce loss of stem cell characteristics, promote neural lineage differentiation and a parallel loss of tumor initiation capacity. Here we show that GSCs retained both neurosphere formation and tumor initiation abilities after short or long term serum exposure. Under serum induced differentiating conditions, GSCs expressed both neural lineage and stem cell markers, highlighting the aberrant pseudo-differentiation state. GSCs maintained under adherent differentiating conditions continued to proliferate and initiate tumor formation with efficiencies similar to GSCs maintained under proliferating (neurosphere) conditions. Proneural (PN) GSCs under serum exposure showed an induction of mesenchymal (MES) gene expression signatures. Our data indicate that the tumor initiation ability of GSCs is independent of their differentiation state and that terminal differentiation as a therapeutic approach may not effectively negate tumorigenicity of GSCs. SIGNIFICANCE Terminal differentiation has been proposed as a therapeutic strategy for glioblastoma (GBM). Culturing of GBM derived tumor initiating glioma stem cells (GSCs) in fetal bovine serum containing media is a proposed mode of differentiation that is thought to induce loss of stem cell characteristics, promote neural lineage differentiation and a parallel loss of tumor initiation capacity. Here we show that GSCs retained both neurosphere formation and tumor initiation abilities after short or long term serum exposure. Under serum induced differentiating conditions, GSCs expressed both neural lineage and stem cell markers, highlighting the aberrant pseudo-differentiation state. GSCs maintained under adherent differentiating conditions continued to proliferate and initiate tumor formation with efficiencies similar to GSCs maintained under proliferating (neurosphere) conditions. Proneural (PN) GSCs under serum exposure showed an induction of mesenchymal (MES) gene expression signatures. Our data indicate that the tumor initiation ability of GSCs is independent of their differentiation state and that terminal differentiation as a therapeutic approach may not effectively negate tumorigenicity of GSCs.
2015-09-01 | GSE58923 | GEO
Project description:SUMMARY Terminal differentiation has been proposed as a therapeutic strategy for glioblastoma (GBM). Culturing of GBM derived tumor initiating glioma stem cells (GSCs) in fetal bovine serum containing media is a proposed mode of differentiation that is thought to induce loss of stem cell characteristics, promote neural lineage differentiation and a parallel loss of tumor initiation capacity. Here we show that GSCs retained both neurosphere formation and tumor initiation abilities after short or long term serum exposure. Under serum induced differentiating conditions, GSCs expressed both neural lineage and stem cell markers, highlighting the aberrant pseudo-differentiation state. GSCs maintained under adherent differentiating conditions continued to proliferate and initiate tumor formation with efficiencies similar to GSCs maintained under proliferating (neurosphere) conditions. Proneural (PN) GSCs under serum exposure showed an induction of mesenchymal (MES) gene expression signatures. Our data indicate that the tumor initiation ability of GSCs is independent of their differentiation state and that terminal differentiation as a therapeutic approach may not effectively negate tumorigenicity of GSCs. SIGNIFICANCE Terminal differentiation has been proposed as a therapeutic strategy for glioblastoma (GBM). Culturing of GBM derived tumor initiating glioma stem cells (GSCs) in fetal bovine serum containing media is a proposed mode of differentiation that is thought to induce loss of stem cell characteristics, promote neural lineage differentiation and a parallel loss of tumor initiation capacity. Here we show that GSCs retained both neurosphere formation and tumor initiation abilities after short or long term serum exposure. Under serum induced differentiating conditions, GSCs expressed both neural lineage and stem cell markers, highlighting the aberrant pseudo-differentiation state. GSCs maintained under adherent differentiating conditions continued to proliferate and initiate tumor formation with efficiencies similar to GSCs maintained under proliferating (neurosphere) conditions. Proneural (PN) GSCs under serum exposure showed an induction of mesenchymal (MES) gene expression signatures. Our data indicate that the tumor initiation ability of GSCs is independent of their differentiation state and that terminal differentiation as a therapeutic approach may not effectively negate tumorigenicity of GSCs.
2015-09-01 | GSE58921 | GEO
Project description:Abnormal activation of stemness factors is a crucial signature of cancer stem cells (CSCs), a highly tumorigenic subpopulation in malignant tumors. However, it is unclear whether multi-signaling pathways are activated in CSCs, as like normal stem cells. I would like to report that an inhibitor of differentiation 1 (ID1) activates intracellular multi-signaling involved in proliferation, genesis, and maintenance of glioma stem cells (GSCs) by suppression of Cullin3, an E3 ubiquitin ligase that degrades Cyclin E and components of SHH and WNT signaling. ID1 inhibits BMP-dependent differentiation of GSCs by activation of BMPR2-targeting miR17/20a. ID1HIGH-Cullin3LOW signature correlates with a poor prognosis of GBM patients with a significant association to gene signatures enriched in EGF, WNT, SHH, and BMP signaling. Combinational inhibition of GSC intracellular multi-signaling network increases tumor-bearing mice survival. These results provide insights on molecular and cellular basis of GSC biology, and also suggest necessity of multi-signaling inhibition for GSCs therapy. Two human primary glioma stem cells (GSCs) such as GSC2 and GSC8 were isolated from two individual primary human glioma specimens. The GSCs were directly transfected with pSuper-GFP-ID1-shRNA and pSuper-GFP-Scrambled-shRNA using FuGENE 6 reagent (Roche). The RNA extraction in these cells was used to analyze gene expression.
2013-09-05 | E-GEOD-40614 | biostudies-arrayexpress
Project description:To identify receptors and pathways active in glioblastoma (GBM) stem like cells (GSCs), we generated and screened thousands of monoclonal antibodies (mAbs) for preferential binding to primary cultures enriched in GSCs. This led to the identification of the integrin alpha 7 (ITGA7) as a major laminin receptor in GSCs and in primary high-grade glioma specimens. Analyses of mRNA profiles in comprehensive datasets revealed that high ITGA7 expression was negatively correlated with survival of patients with both low- and high-grade glioma. In vitro and in vivo analyses demonstrated a key biological function of ITGA7 in growth and invasion of GSCs. In addition, we showed that targeting ITGA7 by RNAi or blocking mAbs impaired laminin-induced signaling and led to a significant delay of tumor engraftment and strong reduction in size and invasion. Our data underline the potential value of ITGA7 as glioma biomarker and therapeutic target.
2018-01-10 | PXD006069 | Pride
Project description:Background: Isocitrate dehydrogenase mutant (IDH-mut) glioma represents a distinct subtype of adult glioma. Although IDH-mut glioma displays slightly better prognosis among adult gliomas, these tumors are still incurable largely due to the lack of effective treatments. Targeting SHP2 has been shown to be a promising therapeutic approach in various types of malignancies, and our previous research demonstrated its efficacy against IDH wildtype (WT) glioblastoma (GBM). However, whether IDH-mutant gliomas are responsive to SHP2 inhibition remains unknown. Methods: Bioinformatic and biological analyses revealed increased expression and activation of PDGFRα-SHP2-ERK pathway in clinical IDH-mutant gliomas and patient-derived IDH-mut glioma stem-like cells (GSCs). Therapeutic effects of a SHP2 inhibitor on inhibition of the PDGFRα-SHP2-ERK signaling and tumorigenicity of IDH-mut GSCs, individually or in combination with radiation therapy (RT) were assessed by cell growth, glioma sphere formation, cell differentiation, flow cytometry, immunoblotting, orthotopic brain tumor xenograft, bioluminescent tracking, and immunohistochemistry. Results: We found a marked increase in PDGFRα expression in clinical IDH-mutant gliomas and IDH-mut GSCs, leading to the activation of the downstream SHP2-ERK pathway. Treatment with a blood-brain barrier-penetrable SHP2 inhibitor, SHP099 significantly inhibited GSC tumorigenic properties in vitro and in vivo by impeding SHP2-ERK axis and inducing cellular differentiation. Additionally, SHP099 treatment synergistically enhanced cytotoxicity of RT on IDH-mut GSCs in vitro and in orthotopic glioma xenografts, the standard treatment for IDH-mut glioma. Mechanistically, the PDGFRα -SHP2-ERK axis is activated in IDH-mut gliomas while radiation activates the SHP2-ERK pathway. Targeting SHP2 suppressed the activated ERK signaling thereby enhancing cytotoxicity of RT against IDH-mut gliomas. Conclusion: Targeting SHP2 in combination with RT for treating IDH-mut glioma displays promising therapeutic efficacy through suppressing a preferentially activated SHP2-ERK axis in IDH-mut gliomas.
2025-09-19 | GSE277548 | GEO
Project description:Glioblastoma (GBM) ranks among the most lethal of human cancers, containing glioma stem cells (GSCs) that display therapeutic resistance. Here, we report that the lncRNA INHEG is highly expressed in GSCs compared to differentiated glioma cells (DGCs) and promotes GSC self-renewal through control of rRNA 2’-O-methylation. INHEG induces the interaction between a novel SUMO E3 ligase TAF15 and NOP58, a core component of snoRNP that guides rRNA methylation, to regulate NOP58 sumoylation and accelerate the C/D box snoRNP assembly. INHEG activation enhances rRNA 2’-O-methylation, thereby increasing the translation of oncogenic proteins including EGFR and IGF1R in glioma cells. Taken together, this study identifies a lncRNA that connects snoRNP-guided rRNA 2’-O-methylation to upregulated protein translation in GSCs, supporting a new axis for potential therapeutic targeting of gliomas.
2023-09-28 | GSE185695 | GEO