naa a22 4500 510746306 CHVBK 20180411083047.0 cr unu---uuuuu 180411e20130901xx s 000 0 eng 10.1007/s12192-013-0414-2 doi (NATIONALLICENCE)springer-10.1007/s12192-013-0414-2 Heat shock protein expression analysis in canine osteosarcoma reveals HSP60 as a potentially relevant therapeutic target [Elektronische Daten] [Gayathri Selvarajah, Floor Bonestroo, Jolle Kirpensteijn, Marja Kik, Ruurd van der Zee, Willem van Eden, Elpetra Timmermans-Sprang, Adri Slob, Jan Mol] Heat shock proteins (HSP) are highly conserved across eukaryotic and prokaryotic species. These proteins play a role in response to cellular stressors, protecting cells from damage and facilitating recovery. In tumor cells, HSPs can have cytoprotective effects and interfere with apoptotic cascades. This study was performed to assess the prognostic and predictive values of the gene expression of HSP family members in canine osteosarcoma (OS) and their potential for targeted therapy. Gene expressions for HSP were assessed using quantitative PCR (qPCR) on 58 snap-frozen primary canine OS tumors and related to clinic-pathological parameters. A significant increased expression of HSP60 was found in relation to shorter overall survival and an osteoblastic phenotype. Therefore, the function of HSP60 was investigated in more detail. Immunohistochemical analysis revealed heterogeneous staining for HSP60 in tumors. The highest immunoreactivity was found in tumors of short surviving dogs. Next HSP expression was shown in a variety of canine and human OS cell lines by qPCR and Western blot. In two highly metastatic cell lines HSP60 expression was silenced using siRNA resulting in decreased cell proliferation and induction of apoptosis in both cell lines. It is concluded that overexpression of HSP60 is associated with a poor prognosis of OS and should be evaluated as a new target for therapy. Cell Stress Society International, 2013 Heat shock proteins (HSP) nationallicence Osteosarcoma nationallicence Dog nationallicence Selvarajah Gayathri Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 104, 3584 CM, Utrecht, The Netherlands aut Bonestroo Floor Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 104, 3584 CM, Utrecht, The Netherlands aut Kirpensteijn Jolle Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 104, 3584 CM, Utrecht, The Netherlands aut Kik Marja Department of Pathobiology, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 1, 3584 CL, Utrecht, The Netherlands aut van der Zee Ruurd Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 1, 3584 CL, Utrecht, The Netherlands aut van Eden Willem Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 1, 3584 CL, Utrecht, The Netherlands aut Timmermans-Sprang Elpetra Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 104, 3584 CM, Utrecht, The Netherlands aut Slob Adri Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 104, 3584 CM, Utrecht, The Netherlands aut Mol Jan Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 104, 3584 CM, Utrecht, The Netherlands aut Cell Stress and Chaperones Springer Netherlands 18/5(2013-09-01), 607-622 1355-8145 18:5<607 2013 18 12192 https://doi.org/10.1007/s12192-013-0414-2 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s12192-013-0414-2 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Selvarajah Gayathri Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 104, 3584 CM, Utrecht, The Netherlands aut NATIONALLICENCE 700 1- Bonestroo Floor Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 104, 3584 CM, Utrecht, The Netherlands aut NATIONALLICENCE 700 1- Kirpensteijn Jolle Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 104, 3584 CM, Utrecht, The Netherlands aut NATIONALLICENCE 700 1- Kik Marja Department of Pathobiology, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 1, 3584 CL, Utrecht, The Netherlands aut NATIONALLICENCE 700 1- van der Zee Ruurd Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 1, 3584 CL, Utrecht, The Netherlands aut NATIONALLICENCE 700 1- van Eden Willem Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 1, 3584 CL, Utrecht, The Netherlands aut NATIONALLICENCE 700 1- Timmermans-Sprang Elpetra Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 104, 3584 CM, Utrecht, The Netherlands aut NATIONALLICENCE 700 1- Slob Adri Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 104, 3584 CM, Utrecht, The Netherlands aut NATIONALLICENCE 700 1- Mol Jan Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 104, 3584 CM, Utrecht, The Netherlands aut NATIONALLICENCE 773 0- Cell Stress and Chaperones Springer Netherlands 18/5(2013-09-01), 607-622 1355-8145 18:5<607 2013 18 12192 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer