Downregulation of PDGFRβ suppresses invasion and migration in osteosarcoma cells by influencing epithelial-mesenchymal transition.

Osteosarcoma (OS) is the most common malignant bone tumor primarily influencing children and adults. Approximately 1/5 of the patients have micrometastasis in the lungs when OS is diagnosed. Platelet-derived growth factor receptor beta (PDGFRβ) is a subtype of platelet-derived growth factor receptor (PDGFR). PDGFRβ has been noted to be highly expressed in OS cell lines and patient specimens and is associated with metastasis and poor prognosis of OS. However, mechanistic insights into the exact role of PDGFRβ in OS pathogenesis and development are still lacking. Here we assessed the effects of PDGFRβ on invasive and migratory abilities, such as the epithelial-mesenchymal transition (EMT) and PI3K, Akt and mTOR pathways in HOS cells. Depleting PDGFRβ resulted in a reduced migration of HOS cells in the si-PDGFRβ group compared to the mock and scramble-treated groups in transwell invasion assays. Using wound-healing assays, we demonstrate the rate of wound healing in the PDGF-BB-stimulated group was higher compared with the mock-treated group. Western blot showed that down-regulation of PDGFRβ decreased the expression of stromal phenotype markers and phosphorylation pathway proteins (PI3K, AKT and mTOR), but the epithelial phenotype marker was increased in HOS cells. Treating HOS cells with PDGF-BB revealed a treatment time-dependent increase of phosphorylated but not total PI3K, AKT, and mTOR. Taken together, we suggest that PDGFRβ plays an important role in OS invasion, migration and EMT by influencing the PI3K, Akt and mTOR pathways, hence highlighting PDGFRβ as a potential therapeutic target for OS.