Project description:To identify a novel miRNA that is aberrantly expressed in GICs, we analyzed differences in miRNA expression between the mouse GICs, NSCL61 and OPCL61, showing characteristic features of cancer stem cell, and their parental cells by miRNA microarrays. neural stem cells, glioma-initiating cells (GICs) from neural stem cells, oligodendrocyte precursor cells, glioma-initiating cells (GICs) from oligodendrocyte precursor cells.
Project description:To identify factors involved in tumorigenicity of glioma-initiating cells (GICs), we compared gene expression in GIC-like cells with and without sox11 expression. We established sox11-expressing mouse glioma-initiating cell (GIC)-like cell line (NSCL61s), NSCL61s-sox11, which lost tumorigenicity when transplanted in vivo. We think that genes, which are differently expressed between NSCL61s and NSCL61s-sox11, would be new targets for glioma therapy.
Project description:Glioblastoma is the deadliest adult brain cancer and all patients ultimately succumb to the disease. Radiation therapy (RT) provides survival benefit of 6 months over surgery alone but these results have not improved in decades. We report that radiation induces a glioma-initiating cell phenotype and identified trifluoperazine (TFP) as a compound that interferes with this phenotype conversion. TFP caused loss of radiation-induced Nanog mRNA expression, activation of GSK3 with consecutive post-translational reduction in p-Akt, Sox2 and -catenin protein levels. TFP did not alter the intrinsic radiation sensitivity of glioma-initiating cells (GICs). Continuous treatment with TFP and a single dose of radiation reduced the number of GICs in vivo and prolonged survival in syngeneic and patient-derived orthotopic xenograft (PDOX) mouse models of glioblastoma. Our findings suggest that combination of a dopamine receptor antagonist with radiation enhances the efficacy of RT in glioblastoma by preventing radiation-induced phenotype conversion of radiosensitive non-GICs into treatment resistant, induced GICs.
Project description:To identify factors involved in glioma-initiating cells (GICs), we compared gene expression between GIC-like cells and non-GICs. Neural stem cells (NSCs) were transfected with pCMS-EGFP-HRasL61 and pBabe-neo by electroporation and cultured in 0.5 mg/ml neomycin. The GFP-positive stable NSCs (NSCL61s) were purified by flow cytometry. Total RNA was prepared using RNeasy Mini Kit (QIAGEN).
Project description:To find factors and pathways that Eva1 regulates in NSCL61 We identified Eva1 as a new factor expressed in glioma-initiating cells (GICs). Eva1 regulates the proliferation of GICs.
Project description:We show that Glioma initiating cells (GICs) can, through MES transition, enter a reactive-astrocyte-like cell state which is connected to increased therapy resistance
