Global gene expression analysis of canine osteosarcoma stem cells reveals a novel role for COX-2 in tumour initiation.

Osteosarcoma is the most common primary bone tumour of both children and dogs. It is an aggressive tumour in both species with a rapid clinical course leading ultimately to metastasis. In dogs and children distant metastasis occurs in >80% of individuals treated by surgery alone. Both canine and...

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Autores principales:	Lisa Y Pang, Emma L Gatenby, Ayako Kamida, Bruce A Whitelaw, Ted R Hupp, David J Argyle
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a741dd22defa4f85af9c8f00ad8d762c
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spelling	oai:doaj.org-article:a741dd22defa4f85af9c8f00ad8d762c2021-11-18T08:38:40ZGlobal gene expression analysis of canine osteosarcoma stem cells reveals a novel role for COX-2 in tumour initiation.1932-620310.1371/journal.pone.0083144https://doaj.org/article/a741dd22defa4f85af9c8f00ad8d762c2014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24416158/?tool=EBIhttps://doaj.org/toc/1932-6203Osteosarcoma is the most common primary bone tumour of both children and dogs. It is an aggressive tumour in both species with a rapid clinical course leading ultimately to metastasis. In dogs and children distant metastasis occurs in >80% of individuals treated by surgery alone. Both canine and human osteosarcoma has been shown to contain a sub-population of cancer stem cells (CSCs), which may drive tumour growth, recurrence and metastasis, suggesting that naturally occurring canine osteosarcoma could act as a preclinical model for the human disease. Here we report the successful isolation of CSCs from primary canine osteosarcoma, as well as established cell lines. We show that these cells can form tumourspheres, and demonstrate relative resistance to chemotherapy. We demonstrate similar results for the human osteosarcma cell lines, U2OS and SAOS2. Utilizing the Affymetrix canine microarray, we are able to definitively show that there are significant differences in global gene expression profiles of isolated osteosarcoma stem cells and the daughter adherent cells. We identified 13,221 significant differences (p = 0.05), and significantly, COX-2 was expressed 141-fold more in CSC spheres than daughter adherent cells. To study the role of COX-2 expression in CSCs we utilized the COX-2 inhibitors meloxicam and mavacoxib. We found that COX-2 inhibition had no effect on CSC growth, or resistance to chemotherapy. However inhibition of COX-2 in daughter cells prevented sphere formation, indicating a potential significant role for COX-2 in tumour initiation.Lisa Y PangEmma L GatenbyAyako KamidaBruce A WhitelawTed R HuppDavid J ArgylePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 1, p e83144 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Lisa Y Pang Emma L Gatenby Ayako Kamida Bruce A Whitelaw Ted R Hupp David J Argyle Global gene expression analysis of canine osteosarcoma stem cells reveals a novel role for COX-2 in tumour initiation.
description	Osteosarcoma is the most common primary bone tumour of both children and dogs. It is an aggressive tumour in both species with a rapid clinical course leading ultimately to metastasis. In dogs and children distant metastasis occurs in >80% of individuals treated by surgery alone. Both canine and human osteosarcoma has been shown to contain a sub-population of cancer stem cells (CSCs), which may drive tumour growth, recurrence and metastasis, suggesting that naturally occurring canine osteosarcoma could act as a preclinical model for the human disease. Here we report the successful isolation of CSCs from primary canine osteosarcoma, as well as established cell lines. We show that these cells can form tumourspheres, and demonstrate relative resistance to chemotherapy. We demonstrate similar results for the human osteosarcma cell lines, U2OS and SAOS2. Utilizing the Affymetrix canine microarray, we are able to definitively show that there are significant differences in global gene expression profiles of isolated osteosarcoma stem cells and the daughter adherent cells. We identified 13,221 significant differences (p = 0.05), and significantly, COX-2 was expressed 141-fold more in CSC spheres than daughter adherent cells. To study the role of COX-2 expression in CSCs we utilized the COX-2 inhibitors meloxicam and mavacoxib. We found that COX-2 inhibition had no effect on CSC growth, or resistance to chemotherapy. However inhibition of COX-2 in daughter cells prevented sphere formation, indicating a potential significant role for COX-2 in tumour initiation.
format	article
author	Lisa Y Pang Emma L Gatenby Ayako Kamida Bruce A Whitelaw Ted R Hupp David J Argyle
author_facet	Lisa Y Pang Emma L Gatenby Ayako Kamida Bruce A Whitelaw Ted R Hupp David J Argyle
author_sort	Lisa Y Pang
title	Global gene expression analysis of canine osteosarcoma stem cells reveals a novel role for COX-2 in tumour initiation.
title_short	Global gene expression analysis of canine osteosarcoma stem cells reveals a novel role for COX-2 in tumour initiation.
title_full	Global gene expression analysis of canine osteosarcoma stem cells reveals a novel role for COX-2 in tumour initiation.
title_fullStr	Global gene expression analysis of canine osteosarcoma stem cells reveals a novel role for COX-2 in tumour initiation.
title_full_unstemmed	Global gene expression analysis of canine osteosarcoma stem cells reveals a novel role for COX-2 in tumour initiation.
title_sort	global gene expression analysis of canine osteosarcoma stem cells reveals a novel role for cox-2 in tumour initiation.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/a741dd22defa4f85af9c8f00ad8d762c
work_keys_str_mv	AT lisaypang globalgeneexpressionanalysisofcanineosteosarcomastemcellsrevealsanovelroleforcox2intumourinitiation AT emmalgatenby globalgeneexpressionanalysisofcanineosteosarcomastemcellsrevealsanovelroleforcox2intumourinitiation AT ayakokamida globalgeneexpressionanalysisofcanineosteosarcomastemcellsrevealsanovelroleforcox2intumourinitiation AT bruceawhitelaw globalgeneexpressionanalysisofcanineosteosarcomastemcellsrevealsanovelroleforcox2intumourinitiation AT tedrhupp globalgeneexpressionanalysisofcanineosteosarcomastemcellsrevealsanovelroleforcox2intumourinitiation AT davidjargyle globalgeneexpressionanalysisofcanineosteosarcomastemcellsrevealsanovelroleforcox2intumourinitiation
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Global gene expression analysis of canine osteosarcoma stem cells reveals a novel role for COX-2 in tumour initiation.

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