PDGFs and PDGFRs in canine osteosarcoma: New targets for innovative therapeutic strategies in comparative oncology
Platelet derived growth factor receptor (PDGFR)α and PDGFRβ are tyrosine kinase receptors that are overexpressed in 70–80% of human osteosarcomas (OSAs) and may be suitable therapeutic targets for specific kinase inhibitors (TKIs). Canine OSA shows histopathological and clinical features similar to...
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| Veröffentlicht in: | The veterinary journal (1997) 2013-01, Vol.195 (1), p.41-47 |
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| container_title | The veterinary journal (1997) |
| container_volume | 195 |
| creator | Maniscalco, Lorella Iussich, Selina Morello, Emanuela Martano, Marina Biolatti, Bartolomeo Riondato, Fulvio Salda, Leonardo Della Romanucci, Mariarita Malatesta, Daniela Bongiovanni, Laura Tirrito, Federica Gattino, Francesca Buracco, Paolo De Maria, Raffaella |
| description | Platelet derived growth factor receptor (PDGFR)α and PDGFRβ are tyrosine kinase receptors that are overexpressed in 70–80% of human osteosarcomas (OSAs) and may be suitable therapeutic targets for specific kinase inhibitors (TKIs). Canine OSA shows histopathological and clinical features similar to human OSA, and is considered an excellent model in comparative oncology. This study investigated PDGF-A, PDGF-B, PDGFRα and PDGFRβ expression in 33 canine OSA samples by immunohistochemistry and in seven primary canine OSA cell lines by Western blot and quantitative PCR analysis.
Immunohistochemical data showed that PDGF-A and PDGF-B are expressed in 42% and 60% of the OSAs analysed, respectively, while PDGFRα and PDGFRβ were expressed in 78% and 81% of cases, respectively. Quantitative PCR data showed that all canine OSA cell lines overexpressed PDGFRα, while 6/7 overexpressed PDGFRβ and PDGF-A relative to a normal osteoblastic cell line. Moreover, in vitro treatment with a specific PDGFR inhibitor, AG1296, caused a dose- and time-dependent decrease in AKT phosphorylation. Collectively, these data show that PDGFRs/PDGFs are co-expressed in canine osteosarcomas, which suggests that an autocrine and/or paracrine loop is involved and that they play an important role in the aetiology of OSA. PDGFRs may be suitable targets for the treatment of canine OSA with a specific TKI. |
| doi_str_mv | 10.1016/j.tvjl.2012.05.003 |
| format | Article |
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Immunohistochemical data showed that PDGF-A and PDGF-B are expressed in 42% and 60% of the OSAs analysed, respectively, while PDGFRα and PDGFRβ were expressed in 78% and 81% of cases, respectively. Quantitative PCR data showed that all canine OSA cell lines overexpressed PDGFRα, while 6/7 overexpressed PDGFRβ and PDGF-A relative to a normal osteoblastic cell line. Moreover, in vitro treatment with a specific PDGFR inhibitor, AG1296, caused a dose- and time-dependent decrease in AKT phosphorylation. Collectively, these data show that PDGFRs/PDGFs are co-expressed in canine osteosarcomas, which suggests that an autocrine and/or paracrine loop is involved and that they play an important role in the aetiology of OSA. PDGFRs may be suitable targets for the treatment of canine OSA with a specific TKI.</description><identifier>ISSN: 1090-0233</identifier><identifier>EISSN: 1532-2971</identifier><identifier>DOI: 10.1016/j.tvjl.2012.05.003</identifier><identifier>PMID: 22704137</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Animals ; Antineoplastic Agents - pharmacology ; Biomarkers, Tumor ; Canine osteosarcoma ; Cell Line, Tumor ; Comparative oncology ; Dog Diseases - genetics ; Dog Diseases - metabolism ; Dogs ; etiology ; Gene Expression Regulation, Neoplastic ; gene overexpression ; histopathology ; humans ; immunohistochemistry ; osteosarcoma ; Osteosarcoma - metabolism ; Osteosarcoma - veterinary ; PDGF ; PDGF receptor ; phosphorylation ; Platelet-Derived Growth Factor - genetics ; Platelet-Derived Growth Factor - metabolism ; quantitative polymerase chain reaction ; receptors ; Receptors, Platelet-Derived Growth Factor - genetics ; Receptors, Platelet-Derived Growth Factor - metabolism ; Targeted therapy ; Western blotting</subject><ispartof>The veterinary journal (1997), 2013-01, Vol.195 (1), p.41-47</ispartof><rights>2012 Elsevier Ltd</rights><rights>Copyright © 2012 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c556t-d2280e2f838a9f47d60a7199373a36c2567cd9b4c50bebf6a975e483df49e3e63</citedby><cites>FETCH-LOGICAL-c556t-d2280e2f838a9f47d60a7199373a36c2567cd9b4c50bebf6a975e483df49e3e63</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.tvjl.2012.05.003$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3548,4022,27922,27923,27924,45994</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22704137$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Maniscalco, Lorella</creatorcontrib><creatorcontrib>Iussich, Selina</creatorcontrib><creatorcontrib>Morello, Emanuela</creatorcontrib><creatorcontrib>Martano, Marina</creatorcontrib><creatorcontrib>Biolatti, Bartolomeo</creatorcontrib><creatorcontrib>Riondato, Fulvio</creatorcontrib><creatorcontrib>Salda, Leonardo Della</creatorcontrib><creatorcontrib>Romanucci, Mariarita</creatorcontrib><creatorcontrib>Malatesta, Daniela</creatorcontrib><creatorcontrib>Bongiovanni, Laura</creatorcontrib><creatorcontrib>Tirrito, Federica</creatorcontrib><creatorcontrib>Gattino, Francesca</creatorcontrib><creatorcontrib>Buracco, Paolo</creatorcontrib><creatorcontrib>De Maria, Raffaella</creatorcontrib><title>PDGFs and PDGFRs in canine osteosarcoma: New targets for innovative therapeutic strategies in comparative oncology</title><title>The veterinary journal (1997)</title><addtitle>Vet J</addtitle><description>Platelet derived growth factor receptor (PDGFR)α and PDGFRβ are tyrosine kinase receptors that are overexpressed in 70–80% of human osteosarcomas (OSAs) and may be suitable therapeutic targets for specific kinase inhibitors (TKIs). Canine OSA shows histopathological and clinical features similar to human OSA, and is considered an excellent model in comparative oncology. This study investigated PDGF-A, PDGF-B, PDGFRα and PDGFRβ expression in 33 canine OSA samples by immunohistochemistry and in seven primary canine OSA cell lines by Western blot and quantitative PCR analysis.
Immunohistochemical data showed that PDGF-A and PDGF-B are expressed in 42% and 60% of the OSAs analysed, respectively, while PDGFRα and PDGFRβ were expressed in 78% and 81% of cases, respectively. Quantitative PCR data showed that all canine OSA cell lines overexpressed PDGFRα, while 6/7 overexpressed PDGFRβ and PDGF-A relative to a normal osteoblastic cell line. Moreover, in vitro treatment with a specific PDGFR inhibitor, AG1296, caused a dose- and time-dependent decrease in AKT phosphorylation. Collectively, these data show that PDGFRs/PDGFs are co-expressed in canine osteosarcomas, which suggests that an autocrine and/or paracrine loop is involved and that they play an important role in the aetiology of OSA. PDGFRs may be suitable targets for the treatment of canine OSA with a specific TKI.</description><subject>Animals</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Biomarkers, Tumor</subject><subject>Canine osteosarcoma</subject><subject>Cell Line, Tumor</subject><subject>Comparative oncology</subject><subject>Dog Diseases - genetics</subject><subject>Dog Diseases - metabolism</subject><subject>Dogs</subject><subject>etiology</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>gene overexpression</subject><subject>histopathology</subject><subject>humans</subject><subject>immunohistochemistry</subject><subject>osteosarcoma</subject><subject>Osteosarcoma - metabolism</subject><subject>Osteosarcoma - veterinary</subject><subject>PDGF</subject><subject>PDGF receptor</subject><subject>phosphorylation</subject><subject>Platelet-Derived Growth Factor - genetics</subject><subject>Platelet-Derived Growth Factor - metabolism</subject><subject>quantitative polymerase chain reaction</subject><subject>receptors</subject><subject>Receptors, Platelet-Derived Growth Factor - genetics</subject><subject>Receptors, Platelet-Derived Growth Factor - metabolism</subject><subject>Targeted therapy</subject><subject>Western blotting</subject><issn>1090-0233</issn><issn>1532-2971</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkU1v1DAQhiMEoh_wBziAj1ySju3YjhEXVGipVNEK6NnyOpPFqyRebO-i_vt6lcIR9WB5Ds-8Gr1PVb2h0FCg8mzT5P1mbBhQ1oBoAPiz6pgKzmqmFX1eZtBQA-P8qDpJaQMAum3Zy-qIMQUt5eq4irefLy8SsXNPDtP3RPxMnJ39jCSkjCHZ6MJkP5Bv-IdkG9eYExlCLNwc9jb7PZL8C6Pd4i57R1KONuPa45IUpq2NCxVmF8awvn9VvRjsmPD1439a3V18-Xn-tb6-ubw6_3RdOyFkrnvGOkA2dLyzemhVL8EqqjVX3HLpmJDK9XrVOgErXA3SaiWw7Xg_tBo5Sn5avV9ytzH83mHKZvLJ4TjaGcMuGSpYaUMw-QSUUyFLmewJKFO8lZqCKChbUBdDShEHs41-svHeUDAHg2ZjDgbNwaABYYrBsvT2MX-3mrD_t_JXWQHeLcBgg7Hr6JO5-1ESBJRXDuwK8XEhsLS79xhNch5nh72P6LLpg__fBQ8kMrWl</recordid><startdate>201301</startdate><enddate>201301</enddate><creator>Maniscalco, Lorella</creator><creator>Iussich, Selina</creator><creator>Morello, Emanuela</creator><creator>Martano, Marina</creator><creator>Biolatti, Bartolomeo</creator><creator>Riondato, Fulvio</creator><creator>Salda, Leonardo Della</creator><creator>Romanucci, Mariarita</creator><creator>Malatesta, Daniela</creator><creator>Bongiovanni, Laura</creator><creator>Tirrito, Federica</creator><creator>Gattino, Francesca</creator><creator>Buracco, Paolo</creator><creator>De Maria, Raffaella</creator><general>Elsevier Ltd</general><scope>FBQ</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7QP</scope></search><sort><creationdate>201301</creationdate><title>PDGFs and PDGFRs in canine osteosarcoma: New targets for innovative therapeutic strategies in comparative oncology</title><author>Maniscalco, Lorella ; Iussich, Selina ; Morello, Emanuela ; Martano, Marina ; Biolatti, Bartolomeo ; Riondato, Fulvio ; Salda, Leonardo Della ; Romanucci, Mariarita ; Malatesta, Daniela ; Bongiovanni, Laura ; Tirrito, Federica ; Gattino, Francesca ; Buracco, Paolo ; De Maria, Raffaella</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c556t-d2280e2f838a9f47d60a7199373a36c2567cd9b4c50bebf6a975e483df49e3e63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Animals</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Biomarkers, Tumor</topic><topic>Canine osteosarcoma</topic><topic>Cell Line, Tumor</topic><topic>Comparative oncology</topic><topic>Dog Diseases - genetics</topic><topic>Dog Diseases - metabolism</topic><topic>Dogs</topic><topic>etiology</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>gene overexpression</topic><topic>histopathology</topic><topic>humans</topic><topic>immunohistochemistry</topic><topic>osteosarcoma</topic><topic>Osteosarcoma - metabolism</topic><topic>Osteosarcoma - veterinary</topic><topic>PDGF</topic><topic>PDGF receptor</topic><topic>phosphorylation</topic><topic>Platelet-Derived Growth Factor - genetics</topic><topic>Platelet-Derived Growth Factor - metabolism</topic><topic>quantitative polymerase chain reaction</topic><topic>receptors</topic><topic>Receptors, Platelet-Derived Growth Factor - genetics</topic><topic>Receptors, Platelet-Derived Growth Factor - metabolism</topic><topic>Targeted therapy</topic><topic>Western blotting</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Maniscalco, Lorella</creatorcontrib><creatorcontrib>Iussich, Selina</creatorcontrib><creatorcontrib>Morello, Emanuela</creatorcontrib><creatorcontrib>Martano, Marina</creatorcontrib><creatorcontrib>Biolatti, Bartolomeo</creatorcontrib><creatorcontrib>Riondato, Fulvio</creatorcontrib><creatorcontrib>Salda, Leonardo Della</creatorcontrib><creatorcontrib>Romanucci, Mariarita</creatorcontrib><creatorcontrib>Malatesta, Daniela</creatorcontrib><creatorcontrib>Bongiovanni, Laura</creatorcontrib><creatorcontrib>Tirrito, Federica</creatorcontrib><creatorcontrib>Gattino, Francesca</creatorcontrib><creatorcontrib>Buracco, Paolo</creatorcontrib><creatorcontrib>De Maria, Raffaella</creatorcontrib><collection>AGRIS</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Calcium & Calcified Tissue Abstracts</collection><jtitle>The veterinary journal (1997)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Maniscalco, Lorella</au><au>Iussich, Selina</au><au>Morello, Emanuela</au><au>Martano, Marina</au><au>Biolatti, Bartolomeo</au><au>Riondato, Fulvio</au><au>Salda, Leonardo Della</au><au>Romanucci, Mariarita</au><au>Malatesta, Daniela</au><au>Bongiovanni, Laura</au><au>Tirrito, Federica</au><au>Gattino, Francesca</au><au>Buracco, Paolo</au><au>De Maria, Raffaella</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>PDGFs and PDGFRs in canine osteosarcoma: New targets for innovative therapeutic strategies in comparative oncology</atitle><jtitle>The veterinary journal (1997)</jtitle><addtitle>Vet J</addtitle><date>2013-01</date><risdate>2013</risdate><volume>195</volume><issue>1</issue><spage>41</spage><epage>47</epage><pages>41-47</pages><issn>1090-0233</issn><eissn>1532-2971</eissn><abstract>Platelet derived growth factor receptor (PDGFR)α and PDGFRβ are tyrosine kinase receptors that are overexpressed in 70–80% of human osteosarcomas (OSAs) and may be suitable therapeutic targets for specific kinase inhibitors (TKIs). Canine OSA shows histopathological and clinical features similar to human OSA, and is considered an excellent model in comparative oncology. This study investigated PDGF-A, PDGF-B, PDGFRα and PDGFRβ expression in 33 canine OSA samples by immunohistochemistry and in seven primary canine OSA cell lines by Western blot and quantitative PCR analysis.
Immunohistochemical data showed that PDGF-A and PDGF-B are expressed in 42% and 60% of the OSAs analysed, respectively, while PDGFRα and PDGFRβ were expressed in 78% and 81% of cases, respectively. Quantitative PCR data showed that all canine OSA cell lines overexpressed PDGFRα, while 6/7 overexpressed PDGFRβ and PDGF-A relative to a normal osteoblastic cell line. Moreover, in vitro treatment with a specific PDGFR inhibitor, AG1296, caused a dose- and time-dependent decrease in AKT phosphorylation. Collectively, these data show that PDGFRs/PDGFs are co-expressed in canine osteosarcomas, which suggests that an autocrine and/or paracrine loop is involved and that they play an important role in the aetiology of OSA. PDGFRs may be suitable targets for the treatment of canine OSA with a specific TKI.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>22704137</pmid><doi>10.1016/j.tvjl.2012.05.003</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | The veterinary journal (1997), 2013-01, Vol.195 (1), p.41-47 |
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| subjects | Animals Antineoplastic Agents - pharmacology Biomarkers, Tumor Canine osteosarcoma Cell Line, Tumor Comparative oncology Dog Diseases - genetics Dog Diseases - metabolism Dogs etiology Gene Expression Regulation, Neoplastic gene overexpression histopathology humans immunohistochemistry osteosarcoma Osteosarcoma - metabolism Osteosarcoma - veterinary PDGF PDGF receptor phosphorylation Platelet-Derived Growth Factor - genetics Platelet-Derived Growth Factor - metabolism quantitative polymerase chain reaction receptors Receptors, Platelet-Derived Growth Factor - genetics Receptors, Platelet-Derived Growth Factor - metabolism Targeted therapy Western blotting |
| title | PDGFs and PDGFRs in canine osteosarcoma: New targets for innovative therapeutic strategies in comparative oncology |
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