Myeloid-derived suppressor cells promote epithelial ovarian cancer cell stemness by inducing the CSF2/p-STAT3 signalling pathway
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ABSTRACT:
PROVIDER: PRJNA607028 | ENA |
REPOSITORIES: ENA
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Project description:Myeloid-derived suppressor cells (MDSCs) are known to contribute to tumour immune escape, studies have verified that MDSCs can induce cancer stem cells (CSCs) and promote tumour immune evasion in breast cancers, cervical cancers and glioblastoma. However, the potential function of MDSCs in regulating CSCs in epithelial ovarian cancer (EOC) progression is unknown. Our results indicated that compared to nonmalignant ovarian patients, EOC patients showed a significantly increased proportion of MDSCs in the peripheral blood. In addition, MDSCs dramatically promoted tumour sphere formation, cell colony formation and CSC accumulation, and MDSCs enhanced the expression of the stemness biomarkers NANOG and c-MYC in EOC cells during co-culture. Moreover, the mechanisms by which MDSCs enhance EOC stemness were further explored, and 586 differentially expressed genes were found in EOC cells co-cultured with or without MDSCs; during co-culture, the expression level of colony stimulating factor 2 (CSF2) was significantly increased in EOC cells co-cultured with MDSCs. Furthermore, the depletion of CSF2 in EOC cells was successfully performed, the promotive effects of MDSCs on EOC cell stemness could be markedly reversed by downregulating CSF2 expression, p-STAT3 signalling pathway molecules were also altered, and the p-STAT3 inhibitor could markedly reverse the promotive effects of MDSCs on EOC cell stemness. In addition, the CSF2 expression level was correlated with EOC clinical staging. Therefore, MDSCs enhance the stemness of epithelial ovarian cancer cells by inducing the CSF2/p-STAT3 signalling pathway. Targeting MDSCs or CSF2 may be a reasonable strategy for enhancing the efficacy of conventional treatments.
2020-12-31 | GSE145374 | GEO
Project description:Myeloid-derived suppressor cells (MDSCs) are known to contribute to tumour immune evasion, and studies have verified that MDSCs can induce cancer stem cells (CSCs) and promote tumour immune evasion in breast cancers, cervical cancers and glioblastoma. However, the potential function of MDSCs in regulating CSCs in epithelial ovarian cancer (EOC) progression is unknown. Our results indicated that compared to nonmalignant ovarian patients, EOC patients showed a significantly increased proportion of MDSCs in the peripheral blood. In addition, MDSCs dramatically promoted tumour sphere formation, cell colony formation and CSC accumulation, and MDSCs enhanced the expression of the stemness biomarkers NANOG and c-MYC in EOC cells during coculture. Moreover, the mechanisms by which MDSCs enhance EOC stemness were further explored, and 586 differentially expressed genes were found in EOC cells cocultured with or without MDSCs; during coculture, the expression level of colony-stimulating factor 2 (CSF2) was significantly increased in EOC cells cocultured with MDSCs. Furthermore, the depletion of CSF2 in EOC cells was successfully performed, the promotive effects of MDSCs on EOC cell stemness could be markedly reversed by downregulating CSF2 expression, p-STAT3 signalling pathway molecules were also altered, and the p-STAT3 inhibitor could markedly reverse the promotive effects of MDSCs on EOC cell stemness. In addition, the CSF2 expression level was correlated with EOC clinical staging. Therefore, MDSCs enhance the stemness of EOC cells by inducing the CSF2/p-STAT3 signalling pathway. Targeting MDSCs or CSF2 may be a reasonable strategy for enhancing the efficacy of conventional treatments. DATABASE: Gene expression data files are available in the GEO databases under the accession number(s) GSE145374.
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Project description:Chicken CSF2 and IL-4-, and CSF2-Dependent Bone Marrow Cultures Represent Macrophages
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Project description:Femur and tibia bones were harvested from 8-week-old wild-type (WT) C57BL/6 mice. Bone marrow was flushed out into cold PBS (Life Technologies) plus 2% heat-inactivated FBS, passed through a needle five times to dissociate the cells, and then passed through a 70-μm cell strainer (Becton Dickinson) to remove cell clumps, bone, hair, and other cells/tissues. After addition of three volumes of NH4Cl solution (0.8% NH4Cl solution; Beyotime Institute of Biotechnology, Jiangsu, China), the mixture was incubated on ice for 10 min to remove red blood cells; the cells were then spun down and resuspended in cold PBS with 2% FBS. The harvested cells were cultured in DMEM containing 10% FBS and supplemented with 10 ng/ml recombinant mouse CSF1 (R&D Systems) or 10 ng/ml recombinant mouse CSF2 (R&D Systems) for 7 days to obtain CSF1- or CSF2-induced BMDMs: M(CSF1) or M(CSF2) cells, respectively. To test the difference genes expression of TAMs obtained from M(CSF1) and M(CSF2) cells in C57BL/6 mice. We used microarrays to detail the global programme of gene expression and identified M(CSF1) and M(CSF2) cells during this process.
2017-02-28 | GSE95404 | GEO
Project description:The work identifies an immune associated cellular, molecular and clinical network involving MDSCs-microRNA101-CtBP2-stem cell core genes, which extrinsically controls cancer stemness and impacts patient outcome. Primary ovarian cancer cells (5 x105) were co-cultured with freshly sorted ovarian cancer associated-MDSCs, peripheral blood lin-CD45+CD33+ cells (5 x105) or medium in a transwell (Corning) for 24 hours. Then, RNA was extracted from the cancer cells by Trizol reagent. The RNAs were applied for microRNA profiling using OpenArray system (Applied Biosystems, Cat# 4470187) (Mestdagh et al., 2008) at University of Michigan Sequencing Core
2013-08-23 | E-GEOD-50082 | biostudies-arrayexpress
Project description:Super-enhancers (SEs) have been recognized as key epigenetic regulators underlying cancer stemness and malignant traits by aberrant transcriptional control and promising therapeutic targets against human cancers. However, the SE landscape and their roles during head and neck squamous cell carcinoma (HNSCC) development especially in cancer stem cells (CSCs) maintenance remain underexplored yet. Here, we identified leukemia inhibitory factor (LIF)-SE as a representative oncogenic SE to activate LIF transcription in HNSCC. LIF secreted from cancer cells and cancer-associated fibroblasts promotes cancer stemness by driving SOX2 transcription in an autocrine or paracrine manner, respectively. Mechanistically, enhancer elements E1, 2, 4 within LIF-SE recruited SOX2/SMAD3/BRD4/EP300 to facilitate LIF transcription; LIF activated downstream LIFR-STAT3 signaling to drive SOX2 transcription, thus forming a previously unknown regulatory feedback loop (LIF-SE-LIF/LIFR-STAT3-SOX2) to maintain LIF overexpression and CSCs stemness. Clinically, increased LIF abundance in clinical samples correlated with malignant clinicopathological features and patient prognosis; higher LIF concentrations in presurgical plasma were negatively associated with patient survival and dramatically diminished following cancer eradication. Therapeutically, pharmacological targeting LIF-SE-LIF/LIFR-STAT3 significantly impaired tumor growth and reduced CSC subpopulations in HNSCC xenograft and PDX models. Our findings reveal a hitherto uncharacterized LIF-SE-mediated auto-regulatory loop in regulating HNSCC stemness and highlight LIF as a novel non-invasive biomarker and potential therapeutic target for HNSCC.
2024-11-06 | GSE274995 | GEO
Project description:Super-enhancers (SEs) have been recognized as key epigenetic regulators underlying cancer stemness and malignant traits by aberrant transcriptional control and promising therapeutic targets against human cancers. However, the SE landscape and their roles during head and neck squamous cell carcinoma (HNSCC) development especially in cancer stem cells (CSCs) maintenance remain underexplored yet. Here, we identified leukemia inhibitory factor (LIF)-SE as a representative oncogenic SE to activate LIF transcription in HNSCC. LIF secreted from cancer cells and cancer-associated fibroblasts promotes cancer stemness by driving SOX2 transcription in an autocrine or paracrine manner, respectively. Mechanistically, enhancer elements E1, 2, 4 within LIF-SE recruited SOX2/SMAD3/BRD4/EP300 to facilitate LIF transcription; LIF activated downstream LIFR-STAT3 signaling to drive SOX2 transcription, thus forming a previously unknown regulatory feedback loop (LIF-SE-LIF/LIFR-STAT3-SOX2) to maintain LIF overexpression and CSCs stemness. Clinically, increased LIF abundance in clinical samples correlated with malignant clinicopathological features and patient prognosis; higher LIF concentrations in presurgical plasma were negatively associated with patient survival and dramatically diminished following cancer eradication. Therapeutically, pharmacological targeting LIF-SE-LIF/LIFR-STAT3 significantly impaired tumor growth and reduced CSC subpopulations in HNSCC xenograft and PDX models. Our findings reveal a hitherto uncharacterized LIF-SE-mediated auto-regulatory loop in regulating HNSCC stemness and highlight LIF as a novel non-invasive biomarker and potential therapeutic target for HNSCC.
2024-11-06 | GSE274994 | GEO
Project description:The work identifies an immune associated cellular, molecular and clinical network involving MDSCs-microRNA101-CtBP2-stem cell core genes, which extrinsically controls cancer stemness and impacts patient outcome.
2013-08-23 | GSE50082 | GEO
Project description:We aimed to study the effects of CSF2 treatment on the transcriptome of the Day 15 female and male embryo. Within the raw files, channel 1= Cy3 and channel 2= Cy5 Transcriptional profiling of bovine extra-embryonic membrane at Day 15 post-insemination produced by IVF. Oocytes were matured and fertilized in vitro using a single Holstein bull. After 5 days in vitro culture, the embryos were either treated with 10 ng/ml bovine recombinant CSF2 or the Control (DPBS/BSA) until Day 7. At Day 7, the embryos were transferred into recipients. At day 15 following insemination, embryos were flushed and collected for total RNA and gDNA extraction. The gender of the embryos were determined by PCR prior to microarray analysis. CSF2 males were compared to Control males while CSF2 females were compared to Control females. Control females were also compared to control males.
2014-10-01 | E-GEOD-55364 | biostudies-arrayexpress
Project description:We aimed to study the effects of CSF2 treatment on the methylome of the Day 15 female and male embryo. Methylomic profiling of bovine extra-embryonic membrane at Day 15 post-insemination produced by IVF. Oocytes were matured and fertilized in vitro using a single Holstein bull. After 5 days in vitro culture, the embryos were either treated with 10 ng/ml bovine recombinant CSF2 or the Control (DPBS/BSA) until Day 7. At Day 7, the embryos were transferred into recipients. At day 15 following insemination, embryos were flushed and collected for total RNA and gDNA extraction. The gender of the embryos were determined by PCR prior to microarray analysis. CSF2 males were compared to Control males while CSF2 females were compared to Control females
2014-10-01 | E-GEOD-55873 | biostudies-arrayexpress