Co-expression of PDGFR Alpha and Beta in Canine Osteosarcomas Cell Lines and Tissues: New Targets for Innovative Therapeutic Strategies.

Introduction: PDGFRα and PDGFRβ are tyrosine kinases receptors overexpressed in 70-80% of human osteosarcoma (OSA) that represent a suitable target for clinical use of specific kinases inhibitors. Canine OSA is considered a model in comparative oncology. In this study we investigated PDGFRα and PDGFRβ expression in canine OSA tissues and primaries canine OSA cell lines.Materials and Methods: PDGFRα and PDGFRβ transcripts was evaluated in 7 OSA cells line by q-PCR. PDGFRα and PDGFRβ expression was evaluated by western blot on 7 cells lines lysates and by immunohistochemistry on 28 cases of canine OSA.Results:Molecular studies revealed that PDGFRα and PDGFRβ transcripts are over-expressed respectively in 4/7 OSA cells line and in 2/7 OSA cell lines if compared to normal osteoblastic cell lines. Immunohistochemistry revealed that canine PDGFRα and PDGFRβ are expressed in 71,4% and 82,1% respectively Conclusion: These data showed that expression and distribution of the PDGFRα and PDGFRβ in canine osteosarcomas are similar to human suggesting the potential therapeutic target of this receptors and remarking the important role of canine model in testing innovative approaches for human osteosarcomas therapies. [...

PDGFs/PDGFRs in canine osteosarcomas: new targets for innovative therapeutical strategies in comparative oncology

PDGFR and PDGFR are tyrosine kinase receptors that are overexpressed in 70-80% of human osteosarcomas (OSAs); thus, they may be suitable targets for the clinical use of specific kinase inhibitors (TKIs). Canine OSA shows histopathological and clinical features similar to those human OSA, and is considered an excellent model in comparative oncology. This study investigated PDGF-A, PDGF-B, PDGFR and PDGFR expression in 33 canine OSA samples by immunohistochemistry and in seven primary canine OSA cell lines by Western blot and q-PCR. The immunohistochemical data showed that PDGF-A and PDGF-B are expressed in 42% and 60% of the OSAs analysed, respectively, while PDGFR and PDGFR were expressed in 78% and 81% of cases, respectively. Quantitative PCR data showed that all canine OSA cell lines overexpressed PDGFRα while 6/7 over expressed 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 the phosphorylation of AKT. The data show that PDGFRs/PDGFs are co-expressed in canine osteosarcomas, which suggests that an autocrine and/or paracrine loop is involved and that these oncogenes play an important role in the aetiology of OSA. Thus, PDGFRs may be suitable targets for the treatment of canine OSA with a specific TKI and may aid in the development of new strategies in human cancer therapy

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 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