Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Canine osteosarcoma cell lines and tissues

ABSTRACT: 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.

ORGANISM(S): Canis lupus familiaris

SUBMITTER: Aaron Sarver

PROVIDER: E-GEOD-27217 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Molecular subtypes of osteosarcoma identified by reducing tumor heterogeneity through an interspecies comparative approach.

Scott Milcah C MC Sarver Aaron L AL Gavin Katherine J KJ Thayanithy Venugopal V Getzy David M DM Newman Robert A RA Cutter Gary R GR Lindblad-Toh Kerstin K Kisseberth William C WC Hunter Lawrence E LE Subramanian Subbaya S Breen Matthew M Modiano Jaime F JF

Bone 20110515 3

The heterogeneous and chaotic nature of osteosarcoma has confounded accurate molecular classification, prognosis, and prediction for this tumor. The occurrence of spontaneous osteosarcoma is largely confined to humans and dogs. While the clinical features are remarkably similar in both species, the organization of dogs into defined breeds provides a more homogeneous genetic background that may increase the likelihood to uncover molecular subtypes for this complex disease. We thus hypothesized th ...[more]

PMID: 21621658

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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.

Dataset Information

Canine osteosarcoma cell lines and tissues

Publications

Molecular subtypes of osteosarcoma identified by reducing tumor heterogeneity through an interspecies comparative approach.

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