PDGFs and PDGFRs in canine osteosarcoma: New targets for innovative therapeutic strategies in comparative oncology

Platelet derived growth factor receptor (PDGFR)alpha and PDGFR beta 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 USA 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, PDGFR alpha and PDGFR beta expression in 33 canine USA samples by immunohistochemistry and in seven primary canine USA 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 PDGFR alpha and PDGFR beta were expressed in 78% and 81% of cases, respectively. Quantitative PCR data showed that all canine USA cell lines overexpressed PDGFR alpha, while 617 overexpressed PDGFR beta 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 USA. PDGFRs may be suitable targets for the treatment of canine USA with a specific TKI. (C) 2012 Elsevier Ltd. All rights reserved.