Down‐regulation of PDGFRβ suppresses invasion and migration in osteosarcoma cells by influencing epithelial–mesenchymal transition

FEBS Open Bio

Xing Liu¹  Jiaqi Guo²  Xiangmei Wu²  Sining Xing²  Huying Tang²  Changdong Wang³  Geli Liu³  Faping Yi³ 

[1] Department of Pediatric Urology Chongqing Children’s Hospital Chongqing Medical University Chongqing China;Department of Physiology Chongqing Medical University Chongqing China;Molecular Medicine and Cancer Research Center Chongqing Medical University Chongqing China;

关键词: epithelial–mesenchymal transition;    invasion;    migration;    osteosarcoma;    PDGFRβ;   

DOI  :  10.1002/2211-5463.12915

来源: DOAJ

【 摘 要 】

Osteosarcoma (OS) is the most common malignant bone tumor primarily influencing children and adults. Approximately one‐fifth of patients have micrometastasis in the lungs when OS is diagnosed. Platelet‐derived growth factor receptor (PDGFR) beta (PDGFRβ) is a subtype of 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 and phosphatidylinositol 3‐kinase (PI3K), Akt and mammalian target of rapamycin (mTOR) pathways in HOS cells. Depleting PDGFRβ resulted in reduced migration of HOS cells in the small interfering RNA duplexes specific for the PDGFRβ group compared with 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 epithelial–mesenchymal transition by influencing the PI3K, Akt and mTOR pathways, hence highlighting PDGFRβ as a potential therapeutic target for OS.

【 授权许可】

Unknown