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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| 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. |
| doi_str_mv | 10.1371/journal.pone.0083144 |
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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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0083144</identifier><identifier>PMID: 24416158</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adherent cells ; Analysis ; Animals ; Biocompatibility ; Biology ; Biotechnology ; Bone cancer ; Bone Neoplasms - enzymology ; Bone Neoplasms - genetics ; Bone Neoplasms - pathology ; Bone Neoplasms - veterinary ; Bone tumors ; Breast cancer ; Cancer ; Cancer metastasis ; Cancer therapies ; Carcinogenesis - genetics ; Carcinogenesis - pathology ; Cell Death - drug effects ; Cell Death - genetics ; Cell Survival - genetics ; Chemotherapy ; Children ; COX-2 inhibitors ; Cyclooxygenase 2 - genetics ; Cyclooxygenase 2 - metabolism ; Cyclooxygenase 2 Inhibitors - pharmacology ; Cyclooxygenase-2 ; DNA microarrays ; Dog Diseases - enzymology ; Dog Diseases - genetics ; Dog Diseases - pathology ; Dogs ; Doxorubicin - pharmacology ; Doxorubicin - therapeutic use ; Drug Resistance, Neoplasm - drug effects ; Drug Resistance, Neoplasm - genetics ; Gene expression ; Gene Expression Regulation, Neoplastic - drug effects ; Genes ; Genetic research ; Humans ; Inhibition ; Kinases ; Medicine ; Meloxicam ; Mesenchymal stem cells ; Metastases ; Metastasis ; Neoplasm Invasiveness ; Neoplastic Stem Cells - drug effects ; Neoplastic Stem Cells - enzymology ; Neoplastic Stem Cells - metabolism ; Neoplastic Stem Cells - pathology ; Osteosarcoma ; Osteosarcoma - enzymology ; Osteosarcoma - genetics ; Osteosarcoma - pathology ; Osteosarcoma - veterinary ; Population ; Sarcoma ; Skin cancer ; Spheres ; Spheroids, Cellular - drug effects ; Spheroids, Cellular - enzymology ; Spheroids, Cellular - pathology ; Stem cells ; Studies ; Surgery ; Tumor Stem Cell Assay ; Tumors ; Veterinary Science</subject><ispartof>PloS one, 2014-01, Vol.9 (1), p.e83144</ispartof><rights>COPYRIGHT 2014 Public Library of Science</rights><rights>2014 Pang et al. 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pang, Lisa Y</au><au>Gatenby, Emma L</au><au>Kamida, Ayako</au><au>Whitelaw, Bruce A</au><au>Hupp, Ted R</au><au>Argyle, David J</au><au>Thamm, Douglas</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Global gene expression analysis of canine osteosarcoma stem cells reveals a novel role for COX-2 in tumour initiation</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2014-01-08</date><risdate>2014</risdate><volume>9</volume><issue>1</issue><spage>e83144</spage><pages>e83144-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>24416158</pmid><doi>10.1371/journal.pone.0083144</doi><tpages>e83144</tpages><oa>free_for_read</oa></addata></record> |
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| recordid | cdi_plos_journals_1476179244 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS); EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Adherent cells Analysis Animals Biocompatibility Biology Biotechnology Bone cancer Bone Neoplasms - enzymology Bone Neoplasms - genetics Bone Neoplasms - pathology Bone Neoplasms - veterinary Bone tumors Breast cancer Cancer Cancer metastasis Cancer therapies Carcinogenesis - genetics Carcinogenesis - pathology Cell Death - drug effects Cell Death - genetics Cell Survival - genetics Chemotherapy Children COX-2 inhibitors Cyclooxygenase 2 - genetics Cyclooxygenase 2 - metabolism Cyclooxygenase 2 Inhibitors - pharmacology Cyclooxygenase-2 DNA microarrays Dog Diseases - enzymology Dog Diseases - genetics Dog Diseases - pathology Dogs Doxorubicin - pharmacology Doxorubicin - therapeutic use Drug Resistance, Neoplasm - drug effects Drug Resistance, Neoplasm - genetics Gene expression Gene Expression Regulation, Neoplastic - drug effects Genes Genetic research Humans Inhibition Kinases Medicine Meloxicam Mesenchymal stem cells Metastases Metastasis Neoplasm Invasiveness Neoplastic Stem Cells - drug effects Neoplastic Stem Cells - enzymology Neoplastic Stem Cells - metabolism Neoplastic Stem Cells - pathology Osteosarcoma Osteosarcoma - enzymology Osteosarcoma - genetics Osteosarcoma - pathology Osteosarcoma - veterinary Population Sarcoma Skin cancer Spheres Spheroids, Cellular - drug effects Spheroids, Cellular - enzymology Spheroids, Cellular - pathology Stem cells Studies Surgery Tumor Stem Cell Assay Tumors Veterinary Science |
| title | Global gene expression analysis of canine osteosarcoma stem cells reveals a novel role for COX-2 in tumour initiation |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-09T01%3A26%3A53IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Global%20gene%20expression%20analysis%20of%20canine%20osteosarcoma%20stem%20cells%20reveals%20a%20novel%20role%20for%20COX-2%20in%20tumour%20initiation&rft.jtitle=PloS%20one&rft.au=Pang,%20Lisa%20Y&rft.date=2014-01-08&rft.volume=9&rft.issue=1&rft.spage=e83144&rft.pages=e83144-&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0083144&rft_dat=%3Cgale_plos_%3EA478874094%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1476179244&rft_id=info:pmid/24416158&rft_galeid=A478874094&rft_doaj_id=oai_doaj_org_article_a741dd22defa4f85af9c8f00ad8d762c&rfr_iscdi=true |