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.
Dipartimento di Patologia Animale sezione Anatomia Patologica, facoltà di Medicina Veterinaria, Università degli Studi di Torino, Via L. Da Vinci, 44 Grugliasco (TO), Italy. lorellamaniscalco@yahoo.it
Lorella
L
Maniscalco
Selina
S
Iussich
Emanuela
E
Morello
Marina
M
Martano
Bartolomeo
B
Biolatti
Fulvio
F
Riondato
Leonardo
L
Della Salda
Mariarita
M
Romanucci
Daniela
D
Malatesta
Laura
L
Bongiovanni
Federica
F
Tirrito
Francesca
F
Gattino
Paolo
P
Buracco
Raffaella
R
De Maria
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D014408:Biomarkers, Tumor; D045744:Cell Line, Tumor; D004283:Dog Diseases / Q000235:genetics / Q000378:metabolism*; D004285:Dogs; D015972:Gene Expression Regulation, Neoplastic; D012516:Osteosarcoma / Q000378:metabolism / Q000662:veterinary*; D010982:Platelet-Derived Growth Factor / Q000235:genetics / Q000378:metabolism*; D017479:Receptors, Platelet-Derived Growth Factor / Q000235:genetics / Q000378:metabolism*
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D010982:Platelet-Derived Growth Factor; D017479:Receptors, Platelet-Derived Growth Factor