Heterotypic mouse models of canine osteosarcoma recapitulate tumor heterogeneity and biological behavior
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ABSTRACT:
OTHER RELATED OMICS DATASETS IN: GSE89835
PROVIDER: PRJNA353505 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR5018840_1.fastq.gz | Fastqsanger.gz | |||
| SRR5018840_2.fastq.gz | Fastqsanger.gz | |||
| SRR5018841_1.fastq.gz | Fastqsanger.gz | |||
| SRR5018841_2.fastq.gz | Fastqsanger.gz | |||
| SRR5018842_1.fastq.gz | Fastqsanger.gz |
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Project description:Purpose: The goals of this study were to establish in vivo models that recapitulated the heterogeneous behavior of osteosarcoma and to develop an approach to distinguish genes expressed from tumor cells apart from those expressed from host cells in next generation sequencing (NGS) data from xenograft tumors. Methods: We used cell lines derived from two spontaneous canine osteosarcoma tumors with distinctly different biological behaviors for heterotypic in vivo modeling. NGS was used to compare the transcriptome profiles of the xenograft tumors to the transcriptome profiles of the parental cell lines and to study the tumor microenvironment of the xenograft tumors. Sequenced reads were trimmed for adaptor sequence, and masked for low-complexity or low-quality sequence, then mapped to a HISAT2 index for mapping which was built from a multi-sequence fasta file containing both the canine (canFam3) and murine (mm10) genomes with the HISAT2 aligner (2.0.2-beta) using default parameters. Rsubread featureCounts (1.4.6) was used to estimate transcript abundance using default parameters. The Bioconductor package ‘edgeR’ (version 3.12.1) was used for differential gene expression analysis and Partek Genomic Suite (version 6.6) was used for clustering and visualization. Qiagen's Ingenuity Pathway Analysis application (version 01-04) and Thomson Reuter's MetaCore software suite were used for pathway and upstream regulator analysis with differentially expressed genes. Results: We document that orthotopic canine osteosarcoma xenografts preserve the biological, molecular, and heterotypic biology observed in the tumors from which they were derived. The data also provide insight into the tumor-host interactions and identify targets that could play a role in treatment strategies. Conclusions: Our study represents the first detailed analysis of xenograft transcriptomes with an approach that allows for accurate examination of tumor-intrinsic properties, as well as organotypic tumor-stromal interaction that may influence tumor progression.
2016-12-07 | GSE89835 | GEO
Project description:Osteosarcoma (OS) is a heterogeneous and rare disease with a disproportionate impact because it mainly affects children and adolescents. Lamentably, more than half of patients with OS succumb to metastatic disease. Clarification of the etiology of the disease, development of better strategies to manage progression, and methods to guide personalized treatments are among the unmet health needs for OS patients. Progress in managing the disease has been hindered by the extreme heterogeneity of OS; thus, better models that accurately recapitulate the natural heterogeneity of the disease are needed. For this study, we used cell lines derived from two spontaneous canine OS tumors with distinctly different biological behavior (OS-1 and OS-2) for heterotypic in vivo modeling that recapitulates the heterogeneous biology and behavior of this disease. Both cell lines demonstrated stability of the transcriptome when grown as orthotopic xenografts in athymic nude mice. Consistent with the behavior of the original tumors, OS-2 xenografts grew more rapidly at the primary site and had greater propensity to disseminate to lung and establish microscopic metastasis. Moreover, OS-2 promoted formation of a different tumor-associated stromal environment than OS-1 xenografts. OS-2-derived tumors comprised a larger percentage of the xenograft tumors than OS-1-derived tumors. In addition, a robust pro-inflammatory population dominated the stromal cell infiltrates in OS-2 xenografts, whereas a mesenchymal population with a gene signature reflecting myogenic signaling dominated those in the OS-1 xenografts. Our studies show that canine OS cell lines maintain intrinsic features of the tumors from which they were derived and recapitulate the heterogeneous biology and behavior of bone cancer in mouse models. This system provides a resource to understand essential interactions between tumor cells and the stromal environment that drive the progression and metastatic propensity of OS.
| S-EPMC5200896 | biostudies-other
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.
2009-11-04 | GSE16087 | GEO
Project description:Osteosarcoma is the most common primary bone tumours of dogs. Canine osteosarcoma contains a sub-population of cancer stem cells. Here we used canine-specific microarrays to compare the global gene expression profiles of osteosarcoma stem cells to adherent cancer cells and canine mesenchymal stem cells.
2013-11-05 | GSE52063 | GEO
Project description:RNA-Seq of canine osteosarcoma tumor samples obtained from Canine Comparative Oncology and Genomics Consortium
2023-08-07 | GSE239948 | 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 dog osteosarcoma and several normal tissues, single channel design, tumor versus normal
2010-05-08 | E-GEOD-16087 | biostudies-arrayexpress
Project description:Background Identification of the molecular determinants of invasion and metastatic potential may guide the development of a rational strategy for devising specific therapies that target the pathways leading to osteosarcoma. Methods In this study, we used pathway-focused GEarrays to screen for candidate genes related to tumor progression. Expression patterns of the selected genes were validated by real time PCR on 61 osteosarcoma patient tumor samples and correlated with clinical and pathological data. Results THBS3, SPARC and SPP1 were identified with pathway-focused GEarrays as genes differentially expressed in osteosarcoma. In particular, THBS3 was expressed at significantly high levels (p=0.0001) in biopsies from patients with metastasis at diagnosis, which is a predictor of worse overall survival, event-free survival and relapse free survival at diagnosis. After chemotherapy, patients with tumors over-expressing THBS3 have worse relapse free survival. High SPARC expression was found in 51 of 55 (96.3%) osteosarcoma samples and correlated with the worst event-free survival (p=0.03) and relapse free survival (p=0.07). Overexpression of SPP1 was found in 47 of 53 (89%) osteosarcomas correlating with better overall survival, event-free survival and relapse free survival at diagnosis. Conclusion With pathway-focused Gearrays, we identified three genes, which interestingly all encode for proteins involved in extracellular remodeling suggesting potential roles in osteosarcoma progression. This is the first report on the THBS3 gene working as a stimulator of tumor progression. Higher levels of THBS3 maintain the capacity of angiogenesis. High levels of SPARC are not required for tumor progression but are necessary for tumor growth and maintenance. SPP1 is not necessary for tumor progression in osteosarcoma and may be associated with inflammatory response and bone remodeling, functioning as a good biomarker. Keywords: disease state analysis using Superarray Pathway focused arrays
2006-06-15 | GSE5045 | GEO
Project description:Cell lines and tumor tissues from canine osteosarcomas with accompanying survival and breed data. Comparisons of gene expression between osteosarcoma-derived cell lines and osteosarcoma tissues.
2011-09-07 | E-GEOD-27217 | 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. This SuperSeries is composed of the SubSeries listed below.
2009-11-04 | GSE16102 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE16087: Gene expression profiles of canine osteosarcoma GSE16088: Gene expression profiles of human osteosarcoma GSE16091: Gene expression profiles of human osteosarcoma, set2 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. Two datasets consisting of canine osteosarcoma tumors, canine osteosarcoma cell lines, and three normal tissues and an analogous human dataset were used to define the similarity between human and canine osteosarcoma. A third dataset, human osteosarcoma with outcome data, was then used to suggest that some of the differences between the canine and human osteosarcoma were, perhaps, related to survival.
2009-11-03 | E-GEOD-16102 | biostudies-arrayexpress