Targeting Innate Immune Signaling in Glioma-Initiating Cells Impairs Self-Renewal and Radiation-Induced Cellular Plasticity
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1204364 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Purpose: Organisms constantly face environmental stressors that threaten their cellular and genomic integrity. In their response, pathogen-associated molecular patterns (PAMPs) and/or damage-associated molecular patterns (DAMPs) are detected by pattern recognition receptors (PRRs) and trigger the innate immune response. In this study we tested the hypothesis that DAMPs contribute to radiation-induced cellular plasticity in Glioblastoma (GBM). GBM is known to be organized hierarchically with a small number of glioma-initiating cells (GICs) driving treatment resistance and recurrences. Materials and Methods: Using patient-derived GBM specimens, we employed sphere forming capacity assays and in vitro extreme limiting dilution assays to examine how innate immune receptor signaling impacts the maintenance and self-renewal of GICs. By leveraging an imaging system for putative GICs we determined de novo induction of GICs from non-stem glioma cells. Results: We find that GIC maintenance after irradiation is mediated by cGAS-independent STING signaling, possibly involving signaling through TLR4 and TLR9. Induction of radiation-induced plasticity involves TLR3 signaling, with potential roles for other receptors and processes modulated by MyD88. Conclusion: These findings suggest that targeting innate immune signaling could prevent radiation-induced cellular plasticity for potential therapeutic benefit.
2025-04-17 | GSE285563 | GEO
Project description:The erythropoietin (EPO) hormone induces red blood cell production and its recombinant form is the most prescribed drug for the treatment of anemia, including that arising in cancer patients. Based on randomized trials showing that EPO administration to cancer patients result in a decreased survival, we investigated the impact of EPO modulation on tumorigenesis. Using genetically engineered mouse models of breast cancer we found that EPO promoted tumorigenesis by activating JAK/STAT signaling specifically in breast tumor initiating cells (TICs) and promoting their self-renewal. Moreover, we define an active role for endogenous EPO in breast cancer progression and breast TIC self-renewal and demonstrate a potential application of EPO pathway inhibition in breast cancer therapy. reference x sample
2014-05-31 | E-GEOD-51433 | biostudies-arrayexpress
Project description:Using established human CRC cell lines, we showed that progastrin expression were enriched under conditions that promote tumor-initiating cells (TIC) self-renewal.
2016-06-29 | E-MTAB-3215 | biostudies-arrayexpress
Project description:The erythropoietin (EPO) hormone induces red blood cell production and its recombinant form is the most prescribed drug for the treatment of anemia, including that arising in cancer patients. Based on randomized trials showing that EPO administration to cancer patients result in a decreased survival, we investigated the impact of EPO modulation on tumorigenesis. Using genetically engineered mouse models of breast cancer we found that EPO promoted tumorigenesis by activating JAK/STAT signaling specifically in breast tumor initiating cells (TICs) and promoting their self-renewal. Moreover, we define an active role for endogenous EPO in breast cancer progression and breast TIC self-renewal and demonstrate a potential application of EPO pathway inhibition in breast cancer therapy.
2014-05-31 | GSE51433 | GEO
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.
2009-11-30 | E-GEOD-17076 | biostudies-arrayexpress
Project description:To identify factors involved in glioma-initiating cells (GICs), we compared gene expressions between GIC-like cells and non-GICs.
2011-06-01 | GSE28091 | GEO
Project description:Glioblastoma multiforme (GBM) is the most common type of brain tumors with dismal outcomes. The mesenchymal phenotype is the hallmark of tumor aggressiveness in GBMs. Perivascular smooth muscle cells (pericytes) are essential in homeostasis of normal and glioma tissues. Here we found HMGA2, an architectural transcription factor that promotes mesenchymal phenotypes in a number of solid tumors, is highly expressed in mesenchymal subtype of GBMs and labels both glioma pericytes and glioma-initiating cells (GICs). Accordingly, depletion of HMGA2 in GICs resulted in compromised self-renewal and tumorigenic capability, as well as undermined mesenchymal or pericyte differentiation. We further showed HMGA2 allows expressions of FOXM1 and PLAU to maintain GIC propagation, gliomagenesis and aggressiveness both in vitro and in vivo. Therefore, suppressing HMGA2-mediated GIC self-renewal and invasiveness might be a promising means to treat GBMs.
| S-EPMC5190103 | biostudies-literature
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.
2015-04-07 | E-GEOD-61080 | biostudies-arrayexpress
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.
2009-12-01 | GSE17076 | GEO
Project description:In the past few years, mammary cancer initiating cells (CICs) have been identified in mouse and human as a subpopulation of tumor cells that selectively posses tumor initiation and self-renewal capacity and the ability to give rise to bulk populations of non-tumorigenic cancer cells progeny through differentiation. They could also be responsible for tumor progression, metastasis, resistance to therapy and recurrence. Thus, the understanding of the pathways regulating CIC self-renewal, differentiation and tumorigenicity represents an important task in the development of effective anticancer therapies. To detect the set of genes associated to CIC in our mouse breast cancer model we analysed three prototypic situations: TUBO cells grown in DMEM under adherent conditions (called TDA in GSE26517 and epithelial bulk in GSE21451), TUBO cells grown in mammosphere medium under adherent conditions (called TMA in GSE26517), TUBO cells grown in mammosphere medium under low-attachment conditions (called mammospheres p1 in GSE21451), i.e. the conditions used to support the formation of mammospheres. This analysis led to the identification of growth factors and immune system-related genes, including toll-like receptor 2 (TLR2). The inhibition of TLR2 signaling pathway strongly impaired mammosphere generation, demonstrating the involvement of TLR2 in CSC self-renewal.
2013-11-30 | GSE26527 | GEO