Feedback modulation of endothelial cells promotes epithelial-mesenchymal transition and metastasis of osteosarcoma cells by Von Willebrand Factor release
Feedback modulation of endothelial cells promotes epithelial-mesenchymal transition and metastasis of osteosarcoma cells by Von Willebrand Factor release
复制标题
内皮细胞的反馈调节通过冯维勒布兰德因子的释放促进骨肉瘤细胞的上皮-间质转化和转移
DOI：
10.1002/jcb.28875
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发表时间：
2019-09-01
影响因子：
4
通讯作者：
Liu, Ling
中科院分区：
文献类型：
--
作者：
Ling, Jing;Sun, Yu;Liu, Ling
血管内皮细胞（EC）作为一种肿瘤小生境细胞，产生并分泌与骨肉瘤（OS）进展相关的血管性血友病因子（VWF）。然而，VWF在OS进展中的作用和调节机制仍不清楚。在这里，使用体外共培养系统，我们表明，内皮细胞促进上皮间质转化（EMT）过程中OS细胞通过增强VWF分泌。内皮细胞分泌的VWF通过激活NF-κ B信号直接参与OS、EMT和转移。此外，OS细胞通过激活磷脂酶D1信号对内皮细胞产生反馈作用，促进VWF的释放，从而导致肿瘤进一步恶化。总之，内皮细胞作为OS的调节剂和效应物，通过VWF释放加速OS恶化。
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-kappa B 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.