Project description:The recently developed COXEN method (PMID: 17666531) has been used to successfully extrapolate gene signatures of drug sensitivity across different tumor histotypes. We wanted to explore the utility of COXEN to predict chemosensitivity in canine cancer, specifically if we could extrapolate gene signatures identified in human datasets over to canine osteosarcoma tumors. This dataset of canine osteosarcoma tumor samples has available clinical outcome data after patients had infected limbs amputated and were treated with doxorubicin and/or carboplatin. We performed microarray analysis on this panel of tumor samples for validating our COXEN prediction models for doxorubicin or carboplatin sensitivity.
Project description:The recently developed COXEN method (PMID: 17666531) has been used to successfully extrapolate gene signatures of drug sensitivity across different tumor histotypes. We wanted to explore the utility of COXEN to predict chemosensitivity in canine cancer, specifically if we could extrapolate gene signatures identified in human datasets over to canine osteosarcoma tumors. This dataset of canine osteosarcoma tumor samples has available clinical outcome data after patients had infected limbs amputated and were treated with doxorubicin and/or carboplatin. We performed microarray analysis on this panel of tumor samples for validating our COXEN prediction models for doxorubicin or carboplatin sensitivity. Chemotherapy naive primary tumors were collected at the time of amputation and archived at the Flint Animal Cancer Center. RNA was extracted from 33 frozen archived tumor samples, followed by microarray analysis. The gene expression data was RMA preprocessed, scaled and were used as a independent test set to evaluate developed prediction models of sensitivity to doxorubicin or carboplatin. Drug predictions were than compared to clinical outcome in these patients that received doxorubicin and/or carboplatin.
Project description:An increased serum alkaline phosphatase concentration is known to be associated with a negative prognosis in canine and human osteosarcoma. To expand upon previous studies regarding the biological relevance of increased serum alkaline phosphatase as a negative prognostic factor, xenogeneic heterotopic transplants were performed using six canine primary osteosarcoma cell lines generated from patients with differing serum alkaline phosphatase concentrations (3 normal and 3 increased). Three of the six cell lines were capable of generating tumors and tumor formation was independent of the serum alkaline phosphatase status of the cell line. Microarray analysis identified 379 genes as being differentially-expressed between the tumorigenic and non-tumorigenic cell lines. Frizzled-6 was up-regulated to the greatest extent (7.78 fold) in tumorigenic cell lines compared to non-tumorigenic cell lines. Frizzled-6, a co-receptor for Wnt ligands has been associated with enhanced tumor-initiating cells and poor prognosis for other tumors. The increased expression of frizzled-6 was confirmed by QPCR and Western blot analysis. Additionally, the tumorigenic cell lines also had an increase in the percentage of side population cells compared to non-tumorigenic cell lines (5.89% versus 1.58%, respectively). There were no differences in tumorigenicity, frizzled-6, or percentage of side population cells noted between osteosarcoma cell lines generated from patients of differing serum alkaline phosphatase concentration. However, to our knowledge this is the first study to identified frizzled-6 as a possible marker of osteosarcoma cell populations with enhanced tumorigenicity and side population cells. Future work will focus on defining the role of frizzled-6 in osteosarcoma tumorigenesis and tumor-initiating cells. A total of six canine primary osteosarcoma cell lines were used in this study. Three cell lines were capable of forming tumors when transplanted into mice (tumorigenic) and three cell lines were not capable of forming tumors upon transplant into mice (non-tumorigenic). The gene expression data is from the primary cell lines, not the transplanted cells. There were no reference cell lines or controls used in this study.
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.
Project description:An increased serum alkaline phosphatase concentration is known to be associated with a negative prognosis in canine and human osteosarcoma. To expand upon previous studies regarding the biological relevance of increased serum alkaline phosphatase as a negative prognostic factor, xenogeneic heterotopic transplants were performed using six canine primary osteosarcoma cell lines generated from patients with differing serum alkaline phosphatase concentrations (3 normal and 3 increased). Three of the six cell lines were capable of generating tumors and tumor formation was independent of the serum alkaline phosphatase status of the cell line. Microarray analysis identified 379 genes as being differentially-expressed between the tumorigenic and non-tumorigenic cell lines. Frizzled-6 was up-regulated to the greatest extent (7.78 fold) in tumorigenic cell lines compared to non-tumorigenic cell lines. Frizzled-6, a co-receptor for Wnt ligands has been associated with enhanced tumor-initiating cells and poor prognosis for other tumors. The increased expression of frizzled-6 was confirmed by QPCR and Western blot analysis. Additionally, the tumorigenic cell lines also had an increase in the percentage of side population cells compared to non-tumorigenic cell lines (5.89% versus 1.58%, respectively). There were no differences in tumorigenicity, frizzled-6, or percentage of side population cells noted between osteosarcoma cell lines generated from patients of differing serum alkaline phosphatase concentration. However, to our knowledge this is the first study to identified frizzled-6 as a possible marker of osteosarcoma cell populations with enhanced tumorigenicity and side population cells. Future work will focus on defining the role of frizzled-6 in osteosarcoma tumorigenesis and tumor-initiating cells.
Project description:Microarrays was performed in 7 aCGH-matched canine primary tumors (4 DLG2 deleted, 3 DLG2 wild type) to investigate the gene expression profiles associated with DLG2 deletion in canine osteosarcoma.
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.
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.
Project description:Osteosarcoma is a rare maligancy seen in pediatric human patients but frequently seen in canine patients. Because of the increased frequecy of osteosarcoma in canines it is becoming recognized as an informative model for human osteosarcoma. Therefore in a better effort to understand the moclular features common to both human and canine osteosracoma a transcriptional mRNA seq dataset of 186 canine osteosarcoma primary tumors
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. Canine osteosarcoma spheres were isolated by their ability to form tumourspheres. Spheres, adherent cells and mesenchymal stem cells were harvested and used for RNA extraction and hybridisation on Affymetrix microarrays (Canine 2.0). Four biological replicates of each sample were included.