IDO1 overexpression significantly affects exosomal miRNA subsets derived from osteosarcoma and ordinary osteoblasts
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE232452 | GEO | 2023/05/14
REPOSITORIES: GEO
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Project description:Seven human osteosarcoma cell lines (U2OS, U2OS/MTX300, HOS, MG63, 143B, ZOS, ZOSM) and the human osteoblast hFOB1.19 were included in the study. Microarray based circRNA expression profiles were acquired using the Arraystar Human circRNA Array (8x15K, Arraystar). We identified circRNAs differentially expressed in human osteosarcoma cell lines compared to human osteoblast hFOB1.19 (control).
2017-04-12 | GSE96964 | GEO
Project description:Analysis of common pediatric osteosarcoma cell lines SaOS2, U2OS and 143B and two patient derived xenograft samples in comparison of osteoblast cell line hFOB1.19.
2022-02-22 | GSE197158 | GEO
Project description:Background Osteosarcoma (OS) is the most common malignant bone tumor in children and adolescents. The survival rate of patients with metastatic disease remains very dismal. Nevertheless, metastasis is a complex process and a single-level analysis is not likely to identify its key biological determinants. In this study, we used a systems biology approach to identify common metastatic pathways that are jointly supported by both mRNA and protein expression data in two distinct human metastatic OS models. Results mRNA expression microarray and N-linked glycoproteomic analyses were performed on two commonly used isogenic pairs of human metastatic OS cell lines, namely HOS/143B and SaOS-2/LM7. Pathway analysis of the differentially regulated genes and glycoproteins separately revealed pathways associated to metastasis including cell cycle regulation, immune response, and epithelial-to-mesenchymal-transition. However, no common significant pathway was found at both genomic and proteomic levels between the two metastatic models, suggesting a very different biological nature of the cell lines. To address this issue, we used a topological significance analysis based on a “shortest path” algorithm to identify topological nodes, which uncovered additional biological information with respect to the genomic and glycoproteomic profiles but remained hidden from the direct analyses. Pathway analysis of the significant topological nodes revealed a striking concordance between the models and identified significant common pathways, including “Cytoskeleton remodeling/TGF/WNT”, “Cytoskeleton remodeling/Cytoskeleton remodeling”, and “Cell adhesion/Chemokines and adhesion”. Of these, the “Cytoskeleton remodeling/TGF/WNT” was the top ranked common pathway from the topological analysis of the genomic and proteomic profiles in the two metastatic models. The up-regulation of proteins in the “Cytoskeleton remodeling/TGF/WNT” pathway in the SaOS-2/LM7 and HOS/143B models was further validated using an orthogonal Reverse Phase Protein Array platform. Conclusions In this study, we used a systems biology approach by integrating genomic and proteomic data to identify key and common metastatic mechanisms in OS. The use of the topological analysis revealed hidden biological pathways that are known to play critical roles in metastasis. Wnt signaling has been previously implicated in OS and other tumors, and inhibitors of Wnt signaling pathways are available for clinical testing. Further characterization of this common pathway and other topological pathways identified from this study may lead to a novel therapeutic strategy for the treatment of metastatic OS. In this study we analyzed two human metastatic OS cell lines and their parental non-metastatic lines. The two human metastatic OS cell line models were HOS/143B and SaOS-2/LM7. The HOS cell line, originally known as M.T. and later as TE-85, was derived from an OS of a 13 year-old girl. The 143B metastatic subline was generated from HOS by a Ki-RAS oncogene transformation [Rhim, J.S., et al., Characterization of human cells transformed in vitro by N-methyl-N'-nitro-N-nitrosoguanidine. Int J Cancer, 1977. 19(4): p. 505-10.]. The SaOS-2 cell was derived from an OS of an 11 year-old girl, and its metastatic subline LM7, was developed by multiple in vivo selection of SaOS-2 cells in mice with pulmonary metastases [Jia, S.F., L.L. Worth, and E.S. Kleinerman, A nude mouse model of human osteosarcoma lung metastases for evaluating new therapeutic strategies. Clin Exp Metastasis, 1999. 17(6): p. 501-6.]. No replicates were included.
2012-04-24 | E-GEOD-37552 | biostudies-arrayexpress
Project description:We investigated how the biologically active form of vitamin D (1,25(OH)2D3) inhibits the epithelial-to-mesenchymal transition (EMT), a critical step in the development of a migratory phenotype in epithelial tumor cells, as well as migration in general, using osteosarcoma (OS) as a model. We looked at how 1,25(OH)2D3 affected pre- and post-EMT migratory states in non-metastatic MG63 and metastatic LM7 OS cell models. In scratch and Boyden chamber assays, 1,25(OH)2D3 inhibited cell migration and invasion, but LM7 cells responded significantly less than MG63 cells (50 vs 26 percent decrease, respectively). 1,25(OH)2D3 inhibited the expression of EMT-inducing genes (e.g., SNAI2) and extracellular contact regulatory genes in MG63 cells but not in LM7 cells (e.g., CD44, MMP3). In comparison to MG63 cells, LM7 cells had significantly lower baseline VDR transcript levels but higher SNAI2 transcript levels. Furthermore, ATAC-seq analysis revealed that 1,25(OH)2D3 epigenetically repressed SNAI2 in MG63 cells, implying that LM7 cells may be constitutively induced to undergo EMT via VDR de-repression mediated by increased SNAI2 levels. Both cell lines appeared to activate an antioxidative pathway involving SOD2 upregulation and concurrent reactive oxygen species (ROS) reduction (e.g., H2O2). ATAC-seq analysis revealed that 1,25(OH)2D3 does not epigenetically regulate SOD2 in MG63 cells, implying a previously unknown indirect link promoting anti-EMT and anti-metastatic oxidation states in both OS cell lines. We studied the fate and migration of mouse hair follicle stem cell progenitor cells after wounding with or without the Vdr because cutaneous wounding and metastasis involve similar signaling factors that regulate cell migration. Conditional loss of Vdr in epithelial progenitor cells promoted cell migration and wound healing in comparison to control animals, indicating that Vdr signaling inhibits cell migration in general. Our findings show that vitamin D signaling inhibits cell migration both in vivo and in vitro, and that inhibiting reactive oxygen species (ROS) in both pre-EMT and post-EMT OS cells is a possible vitamin D mechanism and therapeutic strategy for preventing the onset and progression of OS. MG63 human osteosarcoma cell line treated with vehicle (ethanol) or 1,25(OH)D (10nM) for 24 and 48 hours.
2023-05-01 | GSE220948 | GEO
Project description:To investigate the molecular and cellular alterations occurring in the lung tissue during the pre-metastatic niche formation in osteosarcoma, we used two different approaches in which mice were implanted subcutaneously with the 143B OS cells for a primary tumour (PT) formation or treated with the 143B cell-derived secretome (SCR) to mimic the release of secreted factors by a locally primary tumour.
2023-12-06 | GSE216744 | GEO
Project description:Three osteosarcoma (OS) cell lines (MG-63, Saos-2 and U-2 OS) and 1 osteoblastic cell line (hFOB1.19) were collected for this work. MG-63 was kindly provided by Dr. Agi Grigoriadis from University College London. Saos-2, U-2 OS and hFOB1.19 were purchased from ATCC. All cells used were kept in exponential phase of growth. Total RNA was extracted using the RNeasy Total RNA Isolation kit (QIAGEN). The quality and purity of the products were controlled by Agilent 2100. The final synthesized biotinylated cDNAs were hybridized to Affymetrix GeneChip® U133A 2.0 arrays following the protocol strictly. Arrays were scanned with the Affymetrix scanner 3000. Data analysis was performed by Microarray Suite 5.0 after pre-standard procedure.
2011-09-16 | GSE14789 | GEO
Project description:Three osteosarcoma (OS) cell lines (MG-63, Saos-2 and U-2 OS) and 1 osteoblastic cell line (hFOB1.19) were collected for this work. MG-63 was kindly provided by Dr. Agi Grigoriadis from University College London. Saos-2, U-2 OS and hFOB1.19 were purchased from ATCC. All cells used were kept in exponential phase of growth. Total RNA was extracted using the RNeasy Total RNA Isolation kit (QIAGEN). The quality and purity of the products were controlled by Agilent 2100. The final synthesized biotinylated cDNAs were hybridized to Affymetrix GeneChip® U133A 2.0 arrays following the protocol strictly. Arrays were scanned with the Affymetrix scanner 3000. Data analysis was performed by Microarray Suite 5.0 after pre-standard procedure. Link-test on datasets from both SELDI-TOF-MS and microarray high-throughput analysis platforms can accelerate the identification of tumor biomarkers. The results confirmed that CYC-1 with important biomedical function was an effective candidate biomarker for osteosarcoma early diagnosis.
2011-09-15 | E-GEOD-14789 | biostudies-arrayexpress
Project description:Indoleamine 2, 3-dioxygenase 1 (IDO1) is a metabolic enzyme catalyzing the conversion of the essential amino acid tryptophan to kynurenine. It is induced by IFNg and its expression is linked to poor prognosis across various cancer types. T cells are particularly sensitive to IDO1-dependent tryptophan deprivation in the tumor microenvironment, leading to tumor immune resistance. Therefore, IDO1 inhibitors, such as epacadostat, have been developed, aiming to restore T cell antitumor activity. However, a recent phase III trial assessing the clinical benefit of epacadostat with the PD-1 antibody pembrolizumab in melanoma failed. This prompted us to study the role of IDO1, and the effect of its inhibition, on tumor cells that are under IFNg treatment and T cell attack. We showed that IDO1-mediated tryptophan depletion contributes to the anti-tumor effect of CD8 T cells. Thus, while epacadostat expectedly replenished tryptophan -the desired effect-, this led to adverse protection of melanoma cells from T cell-derived IFNg. RNA sequencing and ribosome profiling of (patient-derived) melanoma cell lines revealed that IFNg caused general protein translation shut down, which was reversed by IDO1 inhibition. Impaired translation was accompanied by an amino acid deprivation-dependent stress response driving ATF4high and MITFlow transcriptomic signatures, which was also observed in melanoma patient tumors. Downregulation of MITF in tumors and PDX- derived cell lines upon treatment was strongly predictive of response to response, to checkpoint blockade-treatment and IFNg, respectively. Conversely, MITF restoration in cultured tumor cells caused T cell resistance. These results highlight the critical role of tryptophan in the melanoma response to T cell-derived IFNg, uncovering an unexpected negative consequence of IDO1 inhibition.
2023-01-16 | GSE198460 | GEO
Project description:<p><strong>OBJECTIVES:</strong> High activity of Indoleamine 2,3-dioxygenase1 (IDO1) in lung cancer patients converts tryptophan (Trp), which is the essential amino acid for T cell metabolism, to kynurenine (Kyn) and consequently suppresses anti-tumor immune responses. We aimed to track the dynamics of IDO1 activity in stage III non-small cell lung cancer (NSCLC) patients who received first-line radiotherapy (RT) and explore its association with survival outcomes.</p><p><strong>MATERIALS AND METHODS:</strong> Systemic IDO1 activity was calculated by Kyn:Trp ratio. Plasma levels of Kyn and Trp in 113 thoracic RT-received stage III NSCLC patients were measured by high-performance liquid chromatography before the initiation of RT. Dynamic change of IDO1 activity was followed in 24 patients by measuring Kyn:Trp ratio before, during and after RT administration.</p><p><strong>RESULTS:</strong> In 24 patients with dynamic tracking of plasma IDO1 activity, there was no significant alterations observed among the 3 time points (Friedman test, p=0.13). The changing pattern of Kyn:Trp ratio was divided into 4 groups: decreased consistently during RT, first increased then decreased, increased consistently, first decreased then increased. Patients whose Kyn:Trp ratio kept decreasing or first increased then decreased were defined as good-change group. The good-change status was identified as an independent positive factor for overall survival (OS) and progression-free survival (PFS) (p=0.04; p=0.01) in multivariate analysis among evaluated parameters. Patients with good change showed significantly superior local control than bad-change group (p=0.01, HR=0.22). In 113 stage III NSCLC patients with pre-radiation Kyn:Trp ratio, a trend that high baseline IDO1 activity was associated with short OS was observed (p=0.079).</p><p><strong>CONCLUSION: </strong>Favorable change of IDO1 activity during RT was associated with superior OS, PFS and local control. IDO1 activity is a promising biomarker for prognosis in stage III NSCLC patients.</p>
2022-08-05 | MTBLS5267 | MetaboLights
Project description:Background Osteosarcoma (OS) is the most common malignant bone tumor in children and adolescents. The survival rate of patients with metastatic disease remains very dismal. Nevertheless, metastasis is a complex process and a single-level analysis is not likely to identify its key biological determinants. In this study, we used a systems biology approach to identify common metastatic pathways that are jointly supported by both mRNA and protein expression data in two distinct human metastatic OS models. Results mRNA expression microarray and N-linked glycoproteomic analyses were performed on two commonly used isogenic pairs of human metastatic OS cell lines, namely HOS/143B and SaOS-2/LM7. Pathway analysis of the differentially regulated genes and glycoproteins separately revealed pathways associated to metastasis including cell cycle regulation, immune response, and epithelial-to-mesenchymal-transition. However, no common significant pathway was found at both genomic and proteomic levels between the two metastatic models, suggesting a very different biological nature of the cell lines. To address this issue, we used a topological significance analysis based on a “shortest path” algorithm to identify topological nodes, which uncovered additional biological information with respect to the genomic and glycoproteomic profiles but remained hidden from the direct analyses. Pathway analysis of the significant topological nodes revealed a striking concordance between the models and identified significant common pathways, including “Cytoskeleton remodeling/TGF/WNT”, “Cytoskeleton remodeling/Cytoskeleton remodeling”, and “Cell adhesion/Chemokines and adhesion”. Of these, the “Cytoskeleton remodeling/TGF/WNT” was the top ranked common pathway from the topological analysis of the genomic and proteomic profiles in the two metastatic models. The up-regulation of proteins in the “Cytoskeleton remodeling/TGF/WNT” pathway in the SaOS-2/LM7 and HOS/143B models was further validated using an orthogonal Reverse Phase Protein Array platform. Conclusions In this study, we used a systems biology approach by integrating genomic and proteomic data to identify key and common metastatic mechanisms in OS. The use of the topological analysis revealed hidden biological pathways that are known to play critical roles in metastasis. Wnt signaling has been previously implicated in OS and other tumors, and inhibitors of Wnt signaling pathways are available for clinical testing. Further characterization of this common pathway and other topological pathways identified from this study may lead to a novel therapeutic strategy for the treatment of metastatic OS.
2012-04-25 | GSE37552 | GEO