Ontology highlight
ABSTRACT:
PROVIDER: PRJNA516866 | ENA |
REPOSITORIES: ENA
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Project description:To identify chromosomal aberrations during passaging of parental SAOS-2 osteosarcoma cells with low metastatic potential and of SAOS-2-derived LM5 cells with increased metastatic potential
2015-05-01 | GSE67125 | GEO
Project description:Purpose: Lung metastasis is responsible for nearly all deaths caused by osteosarcoma, the most common pediatric bone tumor. How malignant bone cells coerce the lung microenvironment to support metastatic growth is unclear. This study delineates how osteosarcoma cells educate the lung microenvironment during metastatic progression. Experimental design: Using single-cell transcriptomics (scRNA-seq), we characterized genome- and tissue-wide molecular changes induced within lung tissues by disseminated osteosarcoma cells in both immunocompetent murine models of metastasis and patient samples. We confirmed transcriptomic findings at the protein level and determined spatial relationships with multi-parameter immunofluorescence. We evaluated the ability of nintedanib to impair metastatic colonization and prevent osteosarcoma-induced education of the lung microenvironment in both immunocompetent murine osteosarcoma and immunodeficient human xenograft models. Results: Osteosarcoma cells induced acute alveolar epithelial injury upon lung dissemination. scRNA-seq demonstrated that the surrounding lung stroma adopts a chronic, non-resolving wound-healing phenotype similar to that seen in other models of lung injury. Accordingly, metastasis-associated lung demonstrated marked fibrosis, likely due to the accumulation of pathogenic, pro-fibrotic, partially-differentiated epithelial intermediates. Inhibitionintermediates. Inhibition of fibrotic pathways with nintedanib prevented metastatic progression in multiple murine and human xenograft models. Conclusions: Our work demonstrates that osteosarcoma cells co-opt fibrosis to promote metastatic outgrowth. When harmonized with data from adult epithelial cancers, our results support a generalized model wherein aberrant mesenchymal-epithelial interactions are critical for promoting lung metastasis. Adult epithelial carcinomas induce fibrotic pathways in normal lung fibroblasts, whereas osteosarcoma, a pediatric mesenchymal tumor, exhibits fibrotic reprogramming in response to the aberrant wound-healing behaviors of an otherwise normal lung epithelium, which are induced by tumor cell interactions.
2024-05-09 | GSE252703 | GEO
Project description:The mechanisms underlying cancer metastasis remain poorly understood. Here, we report that TFAM deficiency rapidly and stably induced spontaneous lung metastasis in mice with liver cancer. Interestingly, unexpected polymerization of nuclear actin was observed in TFAM-knockdown HCC cells when cytoskeleton was examined. Polymerization of nuclear actin is causally linked to the high-metastatic ability of HCC cells by modulating chromatin accessibility and coordinating the expression of genes associated with extracellular matrix remodeling, angiogenesis, and cell migration. Mechanistically, TFAM deficiency blocked the TCA cycle and increased the intracellular malonyl-CoA levels. Malonylation of mDia2, which drives actin assembly, promotes its nuclear translocation. Importantly, inhibition of malonyl-CoA production or nuclear actin polymerization significantly impeded the spread of HCC cells in mice. Moreover, TFAM was significantly downregulated in metastatic HCC tissues and was associated with overall survival and time to tumor recurrence of HCC patients. Taken together, our study connects mitochondria to the metastasis of human cancer via uncovered mitochondria-to-nucleus retrograde signaling, indicating that TFAM may serve as an effective target to block HCC metastasis.
2022-06-23 | MTBLS4307 | MetaboLights
Project description:The Caspase-Activated DNAse drives chromosomal instability and cancer metastasis
| PRJNA649945 | ENA
Project description:Pulmonary metastasis is the main cause of medical failure and death of osteosarcoma patients. Our recent study identified IRX1 as a potential metastasis-driving gene in osteosarcoma. Studies showed that IRX1 can promote the migration, invasion and anoikis resistance of osteosarcoma cells. We generated 143B stable IRX1 knockdown and control cell lines, and found that IRX1 knockdown can inhibit the pulmonary metastasis of 143B cells in orthotopic mouse osteosarcoma model. Expression microarrays are performed in143B-shCtrl and 143B-shIRX1 cells to study the mechanism of IRX1 on promoting metastasis of osteosarcoma
2015-08-25 | E-GEOD-55958 | biostudies-arrayexpress
Project description:Aberrations in the Hedgehog (Hh) pathway are known to related to several malignancies. However, little is known about the function of GLI2, a transcription factor in the Hh pathway, in osteosarcoma. Osteosarcoma is the most frequent primary bone sarcoma in children and adolescents. Despite survival rates of osteosarcoma patients have increased, the prognosis of patients with metastasis remains poor. Therefore, the development of novel therapeutic strategies for osteosarcoma patients is development of novel therapeutic strategies for osteosarcoma patients is urgently needed. Aberrations in the Hedgehog (Hh) pathway are known to related to several malignancies. However, little is known about the function of GLI2, a transcription factor in the Hh pathway, in osteosarcoma. Our findings revealed that GLI2 was overexpressed in osteosarcoma tissues. Additionally, GLI2 is involved in the metastasis of osteosarcoma cells through the regulation of ribosomal protein S3 expression. Furthermore, we showed that arsenic trioxide (ATO) suppressed the invasion and lung metastasis of osteosarcoma cells by the inhibition of GLI transcription. Consequently, these finding reveal a novel function of GLI2 in the metastasis of osteosarcoma and that ATO may be a new therapeutic agentay be a new therapeutic agent. We revealed that a novel function of GLI2 in the metastasis of osteosarcoma and that ATO may be a new therapeutic agent for preventing osteosarcoma metastasis. Negative siRNA(U-2OS) and GLI2 siRNA(U-2OS)
2012-12-14 | E-GEOD-42903 | biostudies-arrayexpress
Project description:Metastasis is the major cause of death in cancer patients, yet the genetic/epigenetic programs that drive metastasis are poorly understood. Here, we report a novel epigenetic reprogramming pathway that is required for breast cancer metastasis. Concerted differential DNA methylation is initiated by activation of the RON receptor tyrosine kinase by its ligand, macrophage stimulating protein (MSP). Through PI3K signaling, RON/MSP promotes expression of the G:T mismatch-specific thymine glycosylase MBD4. RON/MSP and MBD4-dependent aberrant DNA methylation results in misregulation of a specific set of genes. Knockdown of MBD4 reverses methylation at these specific loci, and blocks metastasis. We also show that the MBD4 glycosylase catalytic residue is required for RON/MSP-driven metastasis. Analysis of human breast cancers revealed that this epigenetic program is significantly associated with poor clinical outcome. Furthermore, inhibition of Ron kinase activity with a new pharmacological agent blocks metastasis of patient-derived breast tumor grafts in vivo. To determine the molecular mechanisms by which RON/MSP drives breast cancer metastasis, we performed microarray gene expression profiling of MCF7, MCF7-RON/MSP and MCF7-RON/MSP-shMBD4 cells.
2014-01-02 | E-GEOD-52567 | biostudies-arrayexpress
Project description:Pulmonary metastasis is the main cause of medical failure and death of osteosarcoma patients. Our recent study identified IRX1 as a potential metastasis-driving gene in osteosarcoma. Studies showed that IRX1 can promote the migration, invasion and anoikis resistance of osteosarcoma cells. We generated 143B stable IRX1 knockdown and control cell lines, and found that IRX1 knockdown can inhibit the pulmonary metastasis of 143B cells in orthotopic mouse osteosarcoma model.
2015-08-25 | GSE55958 | GEO
Project description:Pulmonary metastasis continues to be the most common cause of death in osteosarcoma. Indeed, the 5-year survival for newly diagnosed osteosarcoma patients has not significantly changed in over 20 years. Further understanding of the mechanisms of metastasis and resistance for this aggressive pediatric cancer is necessary. Pet dogs naturally develop osteosarcoma providing a novel opportunity to model metastasis development and progression. Given the accelerated biology of canine osteosarcoma, we hypothesized that a direct comparison of canine and pediatric osteosarcoma expression profiles may help identify novel metastasis-associated tumor targets that have been missed through the study of the human cancer alone. Collectively, these data support the strong similarities between human and canine osteosarcoma and underline the opportunities provided by a comparative oncology approach as a means to improve our understanding of cancer biology and therapy. Profiles of human osteosarcoma, single channel design
2009-11-04 | E-GEOD-16091 | biostudies-arrayexpress
Project description:Pulmonary metastasis continues to be the most common cause of death in osteosarcoma. Indeed, the 5-year survival for newly diagnosed osteosarcoma patients has not significantly changed in over 20 years. Further understanding of the mechanisms of metastasis and resistance for this aggressive pediatric cancer is necessary. Pet dogs naturally develop osteosarcoma providing a novel opportunity to model metastasis development and progression. Given the accelerated biology of canine osteosarcoma, we hypothesized that a direct comparison of canine and pediatric osteosarcoma expression profiles may help identify novel metastasis-associated tumor targets that have been missed through the study of the human cancer alone. Collectively, these data support the strong similarities between human and canine osteosarcoma and underline the opportunities provided by a comparative oncology approach as a means to improve our understanding of cancer biology and therapy. Profiles of dog osteosarcoma and several normal tissues, single channel design, tumor versus normal
2010-05-08 | E-GEOD-16087 | biostudies-arrayexpress