Tumour-vasculature development via endothelial-to-mesenchymal transition after radiotherapy controls CD44v6(+) cancer cell and macrophage polarization.
Tumour-vasculature development via endothelial-to-mesenchymal transition after radiotherapy controls CD44v6(+) cancer cell and macrophage polarization.
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放疗后通过内皮细胞向间充质细胞转化的肿瘤血管系统发育控制CD44v6（+）癌细胞和巨噬细胞极化。
DOI：
10.1038/s41467-018-07470-w
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发表时间：
2018-11-30
影响因子：
16.6
通讯作者：
Lee YJ
中科院分区：
文献类型：
--
作者：
Choi SH;Kim AR;Nam JK;Kim JM;Kim JY;Seo HR;Lee HJ;Cho J;Lee YJ
靶向肿瘤血管系统是否能提高放疗疗效仍有争议。我们报告，放射诱导的内皮细胞间质转化（EndMT）导致肿瘤血管与异常SMA+ NG 2+周细胞招聘肿瘤放疗后肿瘤再生长。内皮细胞（EC）中Trp 53（而不是Tgfbr 2）的缺失抑制了放射诱导的EndMT，减少了放射治疗后CD 44 v6+癌症干细胞（CSC）含量高的肿瘤再生长和转移。骨桥蛋白是一种受EC-Trp 53缺失抑制的EndMT相关血管分泌因子，可刺激放射后严重缺氧区域中休眠的CD 44 v6+细胞的增殖。辐射诱导的EndMT显著调节肿瘤相关巨噬细胞（TAM）极化。放射抗性肿瘤EC中CXCR 4的上调与SDF-1+ TAM募集和TAM的M2极化高度相关，而Trp 53缺失抑制了这一点。这些EndMT相关的现象也观察到在照射的人肺癌组织。我们的研究结果表明，靶向肿瘤EndMT可能通过抑制休眠缺氧CSC的重新激活和促进抗肿瘤免疫应答来增强放疗疗效。放射治疗是大多数癌症的主要治疗方法，但目前尚不清楚靶向肿瘤血管系统是否可以增强肿瘤的放射敏感性。在这里，作者表明，放疗后肿瘤内皮-间充质转化导致放射抗性CSC的增殖和肿瘤相关巨噬细胞极化。
It remains controversial whether targeting tumour vasculature can improve radiotherapeutic efficacy. We report that radiation-induced endothelial-to-mesenchymal transition (EndMT) leads to tumour vasculature with abnormal SMA+NG2+ pericyte recruitment during tumour regrowth after radiotherapy. Trp53 (but not Tgfbr2) deletion in endothelial cells (ECs) inhibited radiation-induced EndMT, reducing tumour regrowth and metastases with a high CD44v6+ cancer-stem-cell (CSC) content after radiotherapy. Osteopontin, an EndMT-related angiocrine factor suppressed by EC-Trp53 deletion, stimulated proliferation in dormant CD44v6+ cells in severely hypoxic regions after radiation. Radiation-induced EndMT significantly regulated tumour-associated macrophage (TAM) polarization. CXCR4 upregulation in radioresistant tumour ECs was highly associated with SDF-1+ TAM recruitment and M2 polarization of TAMs, which was suppressed by Trp53 deletion. These EndMT-related phenomena were also observed in irradiated human lung cancer tissues. Our findings suggest that targeting tumour EndMT might enhance radiotherapy efficacy by inhibiting the re-activation of dormant hypoxic CSCs and promoting anti-tumour immune responses. Radiotherapy is the main treatment for most cancer, but it is unclear if targeting tumour vasculature can enhance tumour radiosensitivity. Here, the authors show that tumour endothelial-mesenchymal transition after radiotherapy leads to proliferation of radioresistant CSCs and tumour associated macrophages polarization.
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DOI：
10.1084/jem.20091846
发表时间：
2010-03-15
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Helfrich I;Scheffrahn I;Bartling S;Weis J;von Felbert V;Middleton M;Kato M;Ergün S;Augustin HG;Schadendorf D
通讯作者：
Schadendorf D
影响因子：
5.8
作者：
Gu, Zuguang;Eils, Roland;Schlesner, Matthias
通讯作者：
Schlesner, Matthias
DOI：
10.1158/1078-0432.ccr-16-3122
发表时间：
2017-07-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Brown JM;Recht L;Strober S
通讯作者：
Strober S
影响因子：
11.5
作者：
Choi, Seo-Hyun;Hong, Zhen-Yu;Lee, Yoon-Jin
通讯作者：
Lee, Yoon-Jin
影响因子：
50.3
作者：
Jackson JG;Pant V;Li Q;Chang LL;Quintás-Cardama A;Garza D;Tavana O;Yang P;Manshouri T;Li Y;El-Naggar AK;Lozano G
通讯作者：
Lozano G