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Walter Ingrid

Molecular biomarkers of canine and feline primary osteosarcoma

Abstract: In the dog the osteosarcoma accounts for more than 85% of skeletal tumours. Amputation is the method of choice for controlling a primary appendicular tumour, however, this generally has little effect on long term survival except in the feline species. The analysis of canine and feline osteosarcoma tumour cells has a major advantage over other experimental designs which aim to identify novel biomarkers with crucial function in tumorigenesis and tumour behaviour. Examining the cat ostoesarcoma offers the possibility to study a species that is affected by osteosarcoma, however, does not develop metastases as often, whereas in contrast osteosarcomas in dogs commomly metastasize. Based on this biological conspicuty, we expect a difference in the biomarker profile (matrixmetalloproteinases (MMP´s), ezrin, growth hormone (GR) and growth hormone receptor (GRR), insulin-like-growth factor (IGF), insulin-like-growth- factor binding protein (IGFBP), vascular endothelial growth factors (VEGF), platelet-derived growth factor (PDGF) between cat and dog helping us to identify key factors that contribute to tumor dissemination and the formation of metastases. Using immunohistochemistry, western blotting, zymography and gene expression profiling on tumour cells, should lead to better diagnostic, prognostic and therapeutic tools for the disease. In addition, miRNA´s which are known to regulate gene expression post-transcriptional, are supposed to contribute to cancer. Therefore, we will compare canine and feline mRNA and miRNA profiles in healthy and neoplastic tissue (inlcuding cell lines) to contribute to the knowledge of the role miRNA´s in osteosarcoma. RNA analyisis will be performed by the next generation sequencing method. Moreover, proteome analysis by MALDI-TOF should help to identify proteins that are involved in the metastasizing process. In the future, these informations should lead to a more targeted, individualized therapy of each patient. The VetBioBank, a facility that is engaged in standardized collecting and archiving animal tissue samples (in liquid nitrogen and paraffin) offers the opportunity to apply all histological and molecular biological methods on samples from one patient. In parallel, canine and human osteosarcoma cell lines will be examined with the same panel of methods as described above as they are frequently used for experimental applications. Our results will bring a detailed comparison of biomarkers of the osteosarcoma cells in vivo and in vitro. As the osteosarcoma in dogs is a recognized model for the human osteosarcoma, the results are of interest for the human species and may provide information for diagnostic and therapeutic purposes in clinical oncology as well.

Statistik Austria, science classification: 106023 Molecular biology; 301904 Cancer research; 403014 Veterinary histology; 403017 Veterinary internal medicine

Project leader: Walter Ingrid

Duration: 01.12.10-31.01.15

Type of Research: Basic research

Staff: Steinborn R.,

Vetmed Research Units: VetCore

Funded by: FWF - Fonds zur Förderung der wissenschaftlichen Forschung, Sensengasse 1, 1090 Wien, Austria

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8 Publications