Istituto di Genetica Molecolare-Luigi Luca Cavalli Sforza, UOS Bologna, Consiglio Nazionale Delle Ricerche (IGM-CNR), Bologna, Italy.
IRCCS, Istituto Ortopedico Rizzoli, Bologna, Italy.
J Cell Physiol. 2020 Feb;235(2):1103-1119. doi: 10.1002/jcp.29024. Epub 2019 Jun 25.
Osteosarcoma (OS) is a rare, insidious tumor of mesenchymal origin that most often affects children, adolescents, and young adults. While the primary tumor can be controlled with chemotherapy and surgery, it is the lung metastases that are eventually fatal. Multiple studies into the initial drivers of OS development have been undertaken, but few of these have examined innate immune/inflammatory signaling. A central figure in inflammatory signaling is the innate immune/stress-activated kinase double-stranded RNA-dependent protein kinase (PKR). To characterize the role of PKR in OS, U2OS, and SaOS-2 osteosarcoma cell lines were stably transfected with wild-type or dominant-negative (DN) PKR. Overexpression of PKR enhanced colony formation in soft agar (U2OS and SaOS-2), enhanced cellular migration (U2OS), and invasive migration (SaOS-2). In contrast, overexpression of DN-PKR inhibited attachment-independent growth, migration and/or invasion. These data demonstrate a role for inflammatory signaling in OS formation and migration/invasion and suggest the status of PKR expression/activation may have prognostic value.
骨肉瘤（OS）是一种罕见的、潜伏性的间充质来源的肿瘤，主要发生在儿童、青少年和年轻成年人。虽然原发肿瘤可以通过化疗和手术来控制，但肺部转移最终是致命的。已经进行了多项关于 OS 发展最初驱动因素的研究，但很少有研究检查固有免疫/炎症信号。在炎症信号中，一个核心人物是先天免疫/应激激活激酶双链 RNA 依赖性蛋白激酶（PKR）。为了研究 PKR 在骨肉瘤中的作用，将野生型或显性失活（DN）PKR 稳定转染到 U2OS 和 SaOS-2 骨肉瘤细胞系中。PKR 的过表达增强了软琼脂中的集落形成（U2OS 和 SaOS-2）、增强了细胞迁移（U2OS）和侵袭性迁移（SaOS-2）。相比之下，DN-PKR 的过表达抑制了非依赖性生长、迁移和/或侵袭。这些数据表明炎症信号在 OS 的形成和迁移/浸润中起作用，并表明 PKR 表达/激活的状态可能具有预后价值。
