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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

Gebhard, C; Miller, I; Hummel, K; Neschi Née Ondrovics, M; Schlosser, S; Walter, I (2018): Comparative proteome analysis of monolayer and spheroid culture of canine osteosarcoma cells. J Proteomics. 2018; 177:124-136

Hlavaty, J; Wolfesberger, B; Hauck, M; Obermayer-Pietsch, B; Fuchs-Baumgartinger, A; Miller, I; Walter, I (2017): Ezrin and moesin expression in canine and feline osteosarcoma. Histol Histopathol. 2017; 32(8):805-816

Meyer, FRL; Walter, I (2016): Establishment and Characterization of New Canine and Feline Osteosarcoma Primary Cell Lines. Vet Sci. 2016; 3(2):
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Wolfesberger, B; Fuchs-Baumgartinger, A; Hlavaty, J; Meyer, FR; Hofer, M; Steinborn, R; Gebhard, C; Walter, I (2016): Stem cell growth factor receptor in canine vs. feline osteosarcomas. Oncol Lett. 2016; 12(4):2485-2492
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Gebhard, C; Fuchs-Baumgartinger, A; Razzazi-Fazeli, E; Miller, I; Walter, I (2016): Distribution and activity levels of matrix metalloproteinase 2 and 9 in canine and feline osteosarcoma. Can J Vet Res. 2016; 80(1):66-73 Open Access Logo

Gebhard, C; Gabriel, C; Walter, I (2016): Morphological and Immunohistochemical Characterization of Canine Osteosarcoma Spheroid Cell Cultures. Anat Histol Embryol. 2016; 45(3):219-230
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Meyer, FR; Steinborn, R; Grausgruber, H; Wolfesberger, B; Walter, I (2015): Expression of platelet-derived growth factor BB, erythropoietin and erythropoietin receptor in canine and feline osteosarcoma. Vet J. 2015; 206(1):67-74
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Meyer, FR; Grausgruber, H; Binter, C; Mair, GE; Guelly, C; Vogl, C; Steinborn, R (2013): Cross-platform microarray meta-analysis for the mouse jejunum selects novel reference genes with highly uniform levels of expression. PLoS One. 2013; 8(5):e63125
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