Gene expression analysis of metastatic and non-metastatic osteosarcoma cell lines
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE49003 | GEO | 2013/07/19
SECONDARY ACCESSION(S): PRJNA212559
REPOSITORIES: GEO
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Project description:Analysis of two metastatic OS cell lines, KHOS and KRIB, and two non-metastatic OS cell lines, HOS and U2OS. Results show differences in gene expression between cell lines with different ability to metastasise in vivo. Each of the four cell lines were analyzed in tripicate. Total RNA was extracted from each triplicate cell line culture with Trizol. cRNA was amplified using the Ambion Illumina Total Prep RNA Amplification Kit. Concentration was determined in NanoDrop and qulity checked in the Agilent Bioanalyzer, before hybridizing to Illumina HT-12 BeadChip Array.
2013-07-19 | E-GEOD-49003 | biostudies-arrayexpress
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: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
Project description:Osteosarcoma (OS) is the malignant bone tumor with a high tendency to metastasize to the lung, where the molecular mechanisms are unclear. The mouse OS cell line LM8 has been isolated originally from the Dunn OS cell line by in vivo selection as a subline with a high metastatic potential to the lung. We used gene chip-based global gene expression analysis of differential screening between parental Dunn and LM8 cells in order to reveal genes predominantly expressed in LM8 cells, which correlate with high metastatic potential. 2 cell lines
2011-03-04 | E-GEOD-26648 | biostudies-arrayexpress
Project description:Background: Osteosarcoma (OS) is a very aggressive bone tumor characterized by highly abnormal complex karyotypes. With the improved resolution offered by array comparative genomic hybridization (array CGH) platforms, it is possible to readily detect cryptic microaberrations in genomic DNA. The identification of these microaberrations in genetic syndromes is currently the focus of many array CGH studies, but there have been no analyses to date documenting the occurrence of microaberrations in tumors. Results: In this study we utilized high-resolution oligonucleotide array CGH to identify novel microaberrations under ~750 kb in four OS-derived cell lines: U-2 OS, HOS, MG-63 and SAOS-2. Comparative analysis of these alterations showed that SAOS-2 harbored the most microaberrations at 17, followed by MG-63 with 11, HOS with 9 and U-2 OS with 6. SAOS-2, which has a TP53 mutation, exhibited the highest level of chromosomal instability in previous studies by our group; whereas U-2 OS, which has wild-type p53 status, exhibited the least instability. A consensus region of gain at 5p15.33 was detected in three of the four OS-derived cell lines (HOS, MG-63 and SAOS-2) by aCGH. Of these consensus gains, one was a microaberration of 500 kb in SAOS-2, and confirmed by fluorescence in situ hybridization analysis. It should be noted that this microaberration is immediately telomeric to the TERT gene, which also showed gain. TERT is correlated with increased tumor aggression, as well as decreased progression free survival in OS patients. Keywords: comparative genomic hybridization (array CGH)
2007-12-31 | GSE7077 | GEO
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:Osteosarcoma (OS) is the malignant bone tumor with a high tendency to metastasize to the lung, where the molecular mechanisms are unclear. The mouse OS cell line LM8 has been isolated originally from the Dunn OS cell line by in vivo selection as a subline with a high metastatic potential to the lung. We used gene chip-based global gene expression analysis of differential screening between parental Dunn and LM8 cells in order to reveal genes predominantly expressed in LM8 cells, which correlate with high metastatic potential.
2011-03-04 | GSE26648 | GEO
Project description:Background: Osteosarcoma (OS) is a very aggressive bone tumor characterized by highly abnormal complex karyotypes. With the improved resolution offered by array comparative genomic hybridization (array CGH) platforms, it is possible to readily detect cryptic microaberrations in genomic DNA. The identification of these microaberrations in genetic syndromes is currently the focus of many array CGH studies, but there have been no analyses to date documenting the occurrence of microaberrations in tumors. Results: In this study we utilized high-resolution oligonucleotide array CGH to identify novel microaberrations under ~750 kb in four OS-derived cell lines: U-2 OS, HOS, MG-63 and SAOS-2. Comparative analysis of these alterations showed that SAOS-2 harbored the most microaberrations at 17, followed by MG-63 with 11, HOS with 9 and U-2 OS with 6. SAOS-2, which has a TP53 mutation, exhibited the highest level of chromosomal instability in previous studies by our group; whereas U-2 OS, which has wild-type p53 status, exhibited the least instability. A consensus region of gain at 5p15.33 was detected in three of the four OS-derived cell lines (HOS, MG-63 and SAOS-2) by aCGH. Of these consensus gains, one was a microaberration of 500 kb in SAOS-2, and confirmed by fluorescence in situ hybridization analysis. It should be noted that this microaberration is immediately telomeric to the TERT gene, which also showed gain. TERT is correlated with increased tumor aggression, as well as decreased progression free survival in OS patients. Experiment Overall Design: This genome-wide analysis is the first study to utilize oligonucleotide array CGH to identify microaberrations in OS, likely to contain genes involved in OS tumor oncogenesis. A better understanding of the underlying molecular genetic events leading to tumor initiation and progression could result in the identification of prognostic markers and therapeutic targets.
2008-06-18 | E-GEOD-7077 | biostudies-arrayexpress
Project description:Effective therapies for metastatic osteosarcoma (OS) remain a major clinical unmet need. Targeting mRNA translation in metastatic OS represents an attractive option, as selective translation under stress supports the rapid synthesis of cytoprotective proteins that facilitate metastatic competence. We therefore assessed eukaryotic translation factors in OS, revealing high expression of eIF4A1 in metastatic OS. The eIF4A1 inhibitor, CR-1-31B, potently inhibited metastatic OS growth in vitro and reduced lung tumor burden in orthotopic mouse models. CR-1-31B synergized with the oxidative stress inducer, tert-butylhydroquinone (tBHQ), to enhance cell death under oxidative stress. Proteomic analysis revealed a subset of proteins that were upregulated by tBHQ alone, but inhibited by co-treatment of CR-1-31B, most notably the NRF2 antioxidant transcription factor, and NRF2 inactivation phenocopied CR-1-31B in blocking OS lung metastasis in vivo. Collectively, our data reveal that targeting eIF4A1 with CR-1-31B is highly effective in blocking OS metastasis by blunting the NRF2 antioxidant response.
2024-07-16 | PXD047420 | Pride
Project description:Osteosarcoma (OS) is the most common primary bone tumour in children and young adults, and the second highest cause of cancer-related death in this age group. In spite of aggressive chemotherapy, disease-free survival has not improved significantly in the past 20 years, and 50% of patients subsequently develop fatal pulmonary metastasis. We have performed gene expression profiling of primary osteosarcoma biopsies (i) to identify prognostic markers, and (ii) to identify novel therapeutic targets. Keywords: Comaprison between disease status (metastatic vs non-metastatic) and normal Two-colour experiment. 7 samples for non-metastatic patients, 6 of which are analyzed in duplicate (dye-swaps); 11 samples for metastatic patients, 10 of which are analyzed in duplicate (dye-swaps); 5 samples of non-malignant bone analyzed individualy, no dye-swaps (i.e. 5 biological replicates).
2010-08-30 | E-GEOD-9508 | biostudies-arrayexpress