Schwann Cells Augment Cell Spreading and Metastasis of Lung Cancer
Schwann Cells Augment Cell Spreading and Metastasis of Lung Cancer
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雪旺细胞增强肺癌细胞扩散和转移
DOI：
10.1158/0008-5472.can-18-1702
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发表时间：
2018-10-15
期刊：
影响因子：
11.2
通讯作者：
Shurin, Michael R.
中科院分区：
文献类型：
--
作者：
Zhou, Yan;Shurin, Galina V.;Shurin, Michael R.
虽然肺由周围神经系统（PNS）密集支配，但PNS在肺癌进展中的作用尚不清楚。在这项研究中，我们报告，小鼠成年雪旺细胞（SC），PNS的主要胶质细胞，可以调节肺癌细胞在体外的运动和在体内转移的形成。SC通过增加肿瘤细胞中Snail和Twist的表达来促进两种肺癌细胞系的上皮向间质转化（EMT）和运动;阻断Snail和Twist表达可消除SC诱导的肿瘤细胞运动。SC衍生的CXCL 5负责肺癌细胞中的EMT，因为CXCL 5或其受体CXCR 2的抑制降低了SC诱导的Snail和Twist表达，并降低了肿瘤细胞的运动性。CXCL 5/CXCR 2结合激活了肺癌细胞中的PI 3 K/AKT/GSK-3 β/Snail-Twist信号通路，PI 3 K抑制剂阻断了AKT和GSK-3 β的CXCL 5依赖性磷酸化，降低了Snail/Twist的表达，并限制了肿瘤细胞的侵袭性。在将肿瘤细胞注射到小鼠中之前，肿瘤细胞的SC调节显著增加了局部淋巴结中转移的形成。综上所述，SC可以调节CXCL 5/CXCR 2/PI 3 K/AKT/GSK-3 β/Snail-Twist通路，以促进肺癌细胞的EMT、侵袭力和转移潜力。我们的研究结果揭示了一个新的作用的PNS在肿瘤微环境和肿瘤progress.Significance的功能组织：这项研究增加了我们的理解如何神经，特别是特定的胶质细胞，雪旺细胞，在周围神经系统，可能有助于促进肿瘤的生长和转移。(C)2018年AACR。
Although lungs are densely innervated by the peripheral nervous system (PNS), the role of the PNS in the progression of lung cancer is unknown. In this study, we report that mouse adult Schwann cells (SC), the principal glial cells of the PNS, can regulate the motility of lung cancer cells in vitro and the formation of metastases in vivo. SCs promoted epithelial-to-mesenchymal transition (EMT) and the motility of two lung cancer cell lines by increasing expression of Snail and Twist in tumor cells; blocking of Snail and Twist expression abolished SC-induced motility of tumor cells. SC-derived CXCL5 was responsible for EMT in lung cancer cells, as the inhibition of CXCL5 or its receptor CXCR2 reduced SC-induced expression of Snail and Twist and reduced motility in tumor cells. CXCL5/CXCR2 binding activated the PI3K/AKT/GSK-3 beta/Snail-Twist signaling pathway in lung cancer cells, and the PI3K inhibitor blocked CXCL5-dependent phosphorylation of AKT and GSK-3 beta, reduced expression of Snail/Twist, and limited tumor cell invasiveness. SC conditioning of tumor cells prior to their injection into mice significantly increased the formation of metastases in the regional lymph nodes. In summary, SCs can regulate the CXCL5/CXCR2/PI3K/AKT/GSK-3 beta/Snail-Twist pathway to promote EMT, invasiveness, and metastatic potential of lung cancer cells. Our results reveal a new role of the PNS in the functional organization of the tumor microenvironment and tumor progression.Significance: This study increases our understanding of how nerves and, in particular, specific glial cells, Schwann cells, in the peripheral nervous system, may help promote tumor growth and metastasis. (C) 2018 AACR.