静脉注射
周细胞
CD44细胞
癌症干细胞
转移
癌症研究
外渗
脑转移
肺癌
生物
病理
癌细胞
干细胞
内皮干细胞
癌症
医学
细胞生物学
细胞
生物化学
遗传学
体外
作者
Qian Huang,Liping Liu,Dakai Xiao,Zhi Huang,Wenjun Wang,Kui Zhai,Xiaoguang Fang,Jongmyung Kim,James K. Liu,Wenhua Liang,Jianxing He,Shideng Bao
出处
期刊:Cancer Cell
[Elsevier]
日期:2023-08-17
卷期号:41 (9): 1621-1636.e8
被引量:14
标识
DOI:10.1016/j.ccell.2023.07.012
摘要
Brain metastasis of lung cancer causes high mortality, but the exact mechanisms underlying the metastasis remain unclear. Here we report that vascular pericytes derived from CD44+ lung cancer stem cells (CSCs) in lung adenocarcinoma (ADC) potently cause brain metastases through the G-protein-coupled receptor 124 (GPR124)-enhanced trans-endothelial migration (TEM). CD44+ CSCs in perivascular niches generate the majority of vascular pericytes in lung ADC. CSC-derived pericyte-like cells (Cd-pericytes) exhibit remarkable TEM capacity to effectively intravasate into the vessel lumina, survive in the circulation, extravasate into the brain parenchyma, and then de-differentiate into tumorigenic CSCs to form metastases. Cd-pericytes uniquely express GPR124 that activates Wnt7-β-catenin signaling to enhance TEM capacity of Cd-pericytes for intravasation and extravasation, two critical steps during tumor metastasis. Furthermore, selective disruption of Cd-pericytes, GPR124, or the Wnt7-β-catenin signaling markedly reduces brain and liver metastases of lung ADC. Our findings uncover an unappreciated cellular and molecular paradigm driving tumor metastasis.
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