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Gene expression profiles of glioblastoma tumorspheres cultured in diverse platforms

ABSTRACT: Gene expression profiles of glioblastoma tumorspheres cultured in diverse platforms

PROVIDER: PRJNA1048452 | ENA |

REPOSITORIES: ENA

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Gene expression profiles of glioblastoma tumorspheres cultured in diverse platforms

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Project description:Glioblastoma (GBM), the most prevalent primary brain tumor, remains incurable due to the presence of cancer stem cells (CSC), which can be isolated as tumorspheres (TS) that exhibits classical characteristics of CSCs including stemness and invasiveness. The significantly elevated expression of Bruton’s tyrosine kinase (BTK) in GBM tissues identifies BTK as a potential therapeutic target in GBM. Consequently, ibrutinib, an FDA-approved BTK inhibitor for hematological malignancies, has been repurposed as a candidate for GBM treatment, demonstrating inhibitory effects on proliferation, stemness, and invasiveness of GBM cell lines and TSs. However, its broad-spectrum activity targeting other Tec family kinases and members of the epidermal growth factor receptor (EGFR) family, poses potential life-threatening risks, necessitating the development of more selective alternatives. To address this, BTK selective analogs (SPA1758, SPA1763, SPA8004, SPA8007, SPA8009) were synthesized with the aim of targeting two key characteristics of GBM TSs: stemness and invasiveness. WST and ATP assays identified SPA8007 and SPA8009 as the most effective candidates with superior cytotoxic effects in TSs. Additionally, both SPA8007 and SPA8009 significantly inhibited neurosphere formation and reduced invasiveness in GBM TSs. Furthermore, SPA8007 demonstrated improved survival rates in a GBM xenograft mouse model and reduced the expression of invasiveness markers significantly, as observed in immunohistochemistry (IHC) analysis. These findings highlight SPA8007 as potential novel chemotherapeutic agents with high specificity and efficacy to enhance GBM therapy.

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Expression data from glioblastoma stem-like cells and their differentiated progeny co-cultured with astrocytes

Project description:Glioblastoma stem-like cells or their differentiated progeny were co-cultured for 48h with normal human astrocytes to detect if invasion associated genes were influenced

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mRNA sequencing SUM159PT WT, Kod and KOs cells cultured in adherent or suspension (i.e. secondary tumorspheres) conditions.

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Effect of depletion of conrtol, Rasa1 KO, Nf2 KO, Rasa1 KO, and Rasa1/Nf2 KO in S1 tumorspheres

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