Heat shock protein expression analysis in canine osteosarcoma reveals HSP60 as a potentially relevant therapeutic target

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....

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Main Authors: Selvarajah, Gayathri Thevi, Bonestroo, Floor A. S., Kirpensteijn, Jolle, Kik, Marja J. L., Van der Zee, Ruurd, Van Eden, Willem, Timmermans-Sprang, Elpetra P. M., Slob, Adri, Mol, Jan A.
Format: Article
Language:English
English
Published: Springer Verlag 2013
Online Access:http://psasir.upm.edu.my/id/eprint/29911/1/Heat%20shock%20protein%20expression%20analysis%20in%20canine%20osteosarcoma%20reveals%20HSP60%20as%20a%20potentially%20relevant%20therapeutic%20target.pdf
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author Selvarajah, Gayathri Thevi
Bonestroo, Floor A. S.
Kirpensteijn, Jolle
Kik, Marja J. L.
Van der Zee, Ruurd
Van Eden, Willem
Timmermans-Sprang, Elpetra P. M.
Slob, Adri
Mol, Jan A.
author_facet Selvarajah, Gayathri Thevi
Bonestroo, Floor A. S.
Kirpensteijn, Jolle
Kik, Marja J. L.
Van der Zee, Ruurd
Van Eden, Willem
Timmermans-Sprang, Elpetra P. M.
Slob, Adri
Mol, Jan A.
author_sort Selvarajah, Gayathri Thevi
collection UPM
description 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.
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spelling upm.eprints-299112016-02-05T00:56:41Z http://psasir.upm.edu.my/id/eprint/29911/ Heat shock protein expression analysis in canine osteosarcoma reveals HSP60 as a potentially relevant therapeutic target Selvarajah, Gayathri Thevi Bonestroo, Floor A. S. Kirpensteijn, Jolle Kik, Marja J. L. Van der Zee, Ruurd Van Eden, Willem Timmermans-Sprang, Elpetra P. M. Slob, Adri Mol, Jan A. 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. Springer Verlag 2013 Article PeerReviewed application/pdf en http://psasir.upm.edu.my/id/eprint/29911/1/Heat%20shock%20protein%20expression%20analysis%20in%20canine%20osteosarcoma%20reveals%20HSP60%20as%20a%20potentially%20relevant%20therapeutic%20target.pdf Selvarajah, Gayathri Thevi and Bonestroo, Floor A. S. and Kirpensteijn, Jolle and Kik, Marja J. L. and Van der Zee, Ruurd and Van Eden, Willem and Timmermans-Sprang, Elpetra P. M. and Slob, Adri and Mol, Jan A. (2013) Heat shock protein expression analysis in canine osteosarcoma reveals HSP60 as a potentially relevant therapeutic target. Cell Stress and Chaperones, 18 (5). pp. 607-622. ISSN 1355-8145; ESSN: 1466-1268 10.1007/s12192-013-0414-2 English
spellingShingle Selvarajah, Gayathri Thevi
Bonestroo, Floor A. S.
Kirpensteijn, Jolle
Kik, Marja J. L.
Van der Zee, Ruurd
Van Eden, Willem
Timmermans-Sprang, Elpetra P. M.
Slob, Adri
Mol, Jan A.
Heat shock protein expression analysis in canine osteosarcoma reveals HSP60 as a potentially relevant therapeutic target
title Heat shock protein expression analysis in canine osteosarcoma reveals HSP60 as a potentially relevant therapeutic target
title_full Heat shock protein expression analysis in canine osteosarcoma reveals HSP60 as a potentially relevant therapeutic target
title_fullStr Heat shock protein expression analysis in canine osteosarcoma reveals HSP60 as a potentially relevant therapeutic target
title_full_unstemmed Heat shock protein expression analysis in canine osteosarcoma reveals HSP60 as a potentially relevant therapeutic target
title_short Heat shock protein expression analysis in canine osteosarcoma reveals HSP60 as a potentially relevant therapeutic target
title_sort heat shock protein expression analysis in canine osteosarcoma reveals hsp60 as a potentially relevant therapeutic target
url http://psasir.upm.edu.my/id/eprint/29911/1/Heat%20shock%20protein%20expression%20analysis%20in%20canine%20osteosarcoma%20reveals%20HSP60%20as%20a%20potentially%20relevant%20therapeutic%20target.pdf
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