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.