Down-regulation of PDGFRβ suppresses invasion and migration in osteosarcoma cells by influencing epithelial-mesenchymal transition.,FEBS Open Bio

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Down-regulation of PDGFRβ suppresses invasion and migration in osteosarcoma cells by influencing epithelial-mesenchymal transition.
FEBS Open Bio ( IF 2.8 ) Pub Date : 2020-08-03 , DOI: 10.1002/2211-5463.12915
Sining Xing _{1,

2} , Changdong Wang _{2,

3} , Huying Tang _{1,

2} , Jiaqi Guo _{1,

2} , Xing Liu ₄ , Faping Yi _{2,

3} , Geli Liu _{2,

3} , Xiangmei Wu _{1,

2}

Affiliation

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.

中文翻译：

PDGFRβ 的下调通过影响上皮间质转化来抑制骨肉瘤细胞的侵袭和迁移。

骨肉瘤（OS）是最常见的恶性骨肿瘤，主要影响儿童和成人。当诊断出 OS 时，大约五分之一的患者在肺部有微转移。血小板衍生生长因子受体 (PDGFR) β (PDGFRβ) 是 PDGFR 的一个亚型。PDGFRβ 已被注意到在 OS 细胞系和患者标本中高度表达，并且与 OS 的转移和不良预后相关。然而，仍然缺乏对 PDGFRβ 在 OS 发病机制和发展中的确切作用的机制见解。在这里，我们评估了 PDGFRβ 对侵袭和迁移能力的影响，例如上皮 - 间充质转化和磷脂酰肌醇 3-激酶（PI3K）、Akt 和哺乳动物雷帕霉素靶标（mTOR）通路。在 Transwell 侵袭试验中，与模拟和加扰处理组相比，消耗 PDGFRβ 导致 HOS 细胞在 PDGFRβ 组特异性小干扰 RNA 双链体中的迁移减少。使用伤口愈合试验，我们证明 PDGF-BB 刺激组的伤口愈合率高于模拟治疗组。蛋白质印迹显示，PDGFRβ 的下调降低了基质表型标志物和磷酸化途径蛋白（PI3K、AKT 和 mTOR）的表达，但上皮表型标志物在 HOS 细胞中增加。用 PDGF-BB 处理 HOS 细胞显示磷酸化（但不是全部）PI3K、AKT 和 mTOR 的处理时间依赖性增加。总之，我们认为 PDGFRβ 在 OS 侵袭中起重要作用，

更新日期：2020-08-03

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