OSMR controls glioma stem cell respiration and confers resistance of glioblastoma to ionizing radiation

Sharanek, Ahmad; Burban, Audrey; Laaper, Matthew; Heckel, Émilie; Joyal, Jean‐Sébastien; Soleimani, Vahab D.; Jahani‐Asl, Arezu

doi:10.1038/s41467-020-17885-z

Cited by 57 publications

(37 citation statements)

References 70 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Osm is a cytokine secreted by monocytes/macrophages, and has important regulatory role on bone homeostasis. [37][38][39][40] Osm receptor knockout mice exhibit decreased bone remodeling activity. 34 In a tibial defect model, Osm knockout led to a decrease in osteoblasts number and delayed bone healing.…”

Section: Discussionmentioning

confidence: 99%

Mapping the immune microenvironment for mandibular alveolar bone homeostasis at single-cell resolution

Lin

Zhang

et al. 2021

Bone Res

View full text Add to dashboard Cite

Alveolar bone is the thickened ridge of jaw bone that supports teeth. It is subject to constant occlusal force and pathogens invasion, and is therefore under active bone remodeling and immunomodulation. Alveolar bone holds a distinct niche from long bone considering their different developmental origin and postnatal remodeling pattern. However, a systematic explanation of alveolar bone at single-cell level is still lacking. Here, we construct a single-cell atlas of mouse mandibular alveolar bone through single-cell RNA sequencing (scRNA-seq). A more active immune microenvironment is identified in alveolar bone, with a higher proportion of mature immune cells than in long bone. Among all immune cell populations, the monocyte/macrophage subpopulation most actively interacts with mesenchymal stem cells (MSCs) subpopulation. Alveolar bone monocytes/macrophages express a higher level of Oncostatin M (Osm) compared to long bone, which promotes osteogenic differentiation and inhibits adipogenic differentiation of MSCs. In summary, our study reveals a unique immune microenvironment of alveolar bone, which may provide a more precise immune-modulatory target for therapeutic treatment of oral diseases.

show abstract

Section: Discussionmentioning

confidence: 99%

Mapping the immune microenvironment for mandibular alveolar bone homeostasis at single-cell resolution

Lin

Zhang

et al. 2021

Bone Res

View full text Add to dashboard Cite

show abstract

“…It can induce neurogenesis in prostate cancer, thus promoting cancer growth and migration ( Ding et al, 2013 ). The cytokine receptor for oncostatin M (OSMR) regulates self-renewing brain tumor stem cells and promotes the resistance of GBM to ionizing radiation ( Sharanek et al, 2020 ). In breast cancer, BMPR1-knockdown can inhibit RANKL production through p38 pathway, thereby inhibiting breast cancer-induced osteolysis ( Liu Y. et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

Expression Profile Analysis Identifies a Novel Seven Immune-Related Gene Signature to Improve Prognosis Prediction of Glioblastoma

Han

Cheng

et al. 2021

Front. Genet.

View full text Add to dashboard Cite

Glioblastoma multiform (GBM) is a malignant central nervous system cancer with dismal prognosis despite conventional therapies. Scientists have great interest in using immunotherapy for treating GBM because it has shown remarkable potential in many solid tumors, including melanoma, non-small cell lung cancer, and renal cell carcinoma. The gene expression patterns, clinical data of GBM individuals from the Cancer Genome Atlas database (TCGA), and immune-related genes (IRGs) from ImmPort were used to identify differentially expressed IRGs through the Wilcoxon rank-sum test. The association between each IRG and overall survival (OS) of patients was investigated by the univariate Cox regression analysis. LASSO Cox regression assessment was conducted to explore the prognostic potential of the IRGs of GBM and construct a risk score formula. A Kaplan–Meier curve was created to estimate the prognostic role of IRGs. The efficiency of the model was examined according to the area under the receiver operating characteristic (ROC) curve. The TCGA internal dataset and two GEO external datasets were used for model verification. We evaluated IRG expression in GBM and generated a risk model to estimate the prognosis of GBM individuals with seven optimal prognostic expressed IRGs. A landscape of 22 types of tumor-infiltrating immune cells (TIICs) in glioblastoma was identified, and we investigated the link between the seven IRGs and the immune checkpoints. Furthermore, there was a correlation between the IRGs and the infiltration level in GBM. Our data suggested that the seven IRGs identified in this study are not only significant prognostic predictors in GBM patients but can also be utilized to investigate the developmental mechanisms of GBM and in the design of personalized treatments for them.

show abstract

“…Its receptor is expressed by GSCs in mitochondria and interacts with complex I to promote OXPHOS. Deletion of the oncostatin M receptor reduces OXPHOS, increases ROS levels, and sensitizes GSCs to irradiation [ 71 ]. IL-6 itself induces CD133 expression via the transfer of STAT3 into the nucleus in hypoxic conditions [ 72 ].…”

Section: Energy Metabolism In Idh1wt Gscsmentioning

confidence: 99%

Energy Metabolism in IDH1 Wild-Type and IDH1-Mutated Glioblastoma Stem Cells: A Novel Target for Therapy?

Noorden

Hira

Dijck

et al. 2021

Cells

View full text Add to dashboard Cite

Cancer is a redox disease. Low levels of reactive oxygen species (ROS) are beneficial for cells and have anti-cancer effects. ROS are produced in the mitochondria during ATP production by oxidative phosphorylation (OXPHOS). In the present review, we describe ATP production in primary brain tumors, glioblastoma, in relation to ROS production. Differentiated glioblastoma cells mainly use glycolysis for ATP production (aerobic glycolysis) without ROS production, whereas glioblastoma stem cells (GSCs) in hypoxic periarteriolar niches use OXPHOS for ATP and ROS production, which is modest because of the hypoxia and quiescence of GSCs. In a significant proportion of glioblastoma, isocitrate dehydrogenase 1 (IDH1) is mutated, causing metabolic rewiring, and all cancer cells use OXPHOS for ATP and ROS production. Systemic therapeutic inhibition of glycolysis is not an option as clinical trials have shown ineffectiveness or unwanted side effects. We argue that systemic therapeutic inhibition of OXPHOS is not an option either because the anti-cancer effects of ROS production in healthy cells is inhibited as well. Therefore, we advocate to remove GSCs out of their hypoxic niches by the inhibition of their binding to niches to enable their differentiation and thus increase their sensitivity to radiotherapy and/or chemotherapy.

show abstract

OSMR controls glioma stem cell respiration and confers resistance of glioblastoma to ionizing radiation

Cited by 57 publications

References 70 publications

Mapping the immune microenvironment for mandibular alveolar bone homeostasis at single-cell resolution

Mapping the immune microenvironment for mandibular alveolar bone homeostasis at single-cell resolution

Expression Profile Analysis Identifies a Novel Seven Immune-Related Gene Signature to Improve Prognosis Prediction of Glioblastoma

Energy Metabolism in IDH1 Wild-Type and IDH1-Mutated Glioblastoma Stem Cells: A Novel Target for Therapy?

Contact Info

Product

Resources

About