Department of Hematology and Oncology, Children's Hospital of Soochow University, Suzhou, China.
Department of Hematology, Second Affiliated Hospital of Soochow University, Suzhou, China.
J Cell Biochem. 2019 Sep;120(9):15971-15979. doi: 10.1002/jcb.28875. Epub 2019 May 17.
Endothelial cells (ECs), as a tumor niche cell, generate and secrete Von Willebrand factor (VWF) that is linked to osteosarcoma (OS) progression. However, the role and regulatory mechanisms of VWF that underpin OS progression remain unclear. Here, using a coculture system ex vivo, we showed that ECs promoted the epithelial-mesenchymal transition (EMT) process in OS cells via enhanced VWF secretion. VWF secreted by ECs directly contributed to OS EMT and metastasis by activating NF-κB signaling. In addition, OS cells exerted a feedback effect on ECs to promote VWF release via activation of phospholipase D 1 signaling, through which enhanced VWF secretion results in further tumor deterioration. To conclude, ECs served as a modulator and an effector of OS, accelerating OS exacerbation by VWF release.
内皮细胞（ECs）作为肿瘤微环境中的一种细胞，会生成和分泌与骨肉瘤（OS）进展相关的血管性血友病因子（VWF）。然而，VWF 在 OS 进展中的作用及其调控机制仍不清楚。在这里，我们通过体外共培养系统发现，内皮细胞通过增强 VWF 分泌促进 OS 细胞的上皮间质转化（EMT）过程。内皮细胞分泌的 VWF 通过激活 NF-κB 信号直接促进 OS EMT 和转移。此外，OS 细胞通过激活磷脂酶 D1 信号对内皮细胞施加反馈作用，促进 VWF 的释放，通过这种方式增强 VWF 的分泌会导致肿瘤进一步恶化。总之，内皮细胞作为 OS 的调节剂和效应器，通过释放 VWF 加速 OS 的恶化。
