Real-time imaging reveals the single steps of brain metastasis formation
Real-time imaging reveals the single steps of brain metastasis formation
复制标题
实时成像揭示脑转移瘤形成的单一步骤
DOI：
10.1038/nm.2072
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发表时间：
2010-01-01
期刊：
影响因子：
82.9
通讯作者：
Winkler, Frank
中科院分区：
文献类型：
--
作者：
Kienast, Yvonne;von Baumgarten, Louisa;Winkler, Frank
脑转移经常发生在癌症患者中，并且通常是致命的。我们使用多光子激光扫描显微镜对转移形成的单个步骤进行真实的实时成像。因此，有可能在几分钟到几个月的时间内跟踪体内单个转移癌细胞与小鼠大脑深处血管的关系。在该模型中的基本步骤是在血管分支点停止、早期外渗、与微血管的持续紧密接触以及通过血管共选择（黑色素瘤）或早期血管生成（肺癌）的血管周围生长。不同肿瘤类型的无效步骤不同。长期休眠只观察到单个血管周围癌细胞，其中一些不断移动。血管内皮生长因子-A（VEGF-A）抑制剂通过阻止血管生成生长至大转移而诱导肺癌微转移的长期休眠。在体内成像脑转移瘤建立的能力为它们的演变和对治疗的反应提供了新的见解。
Brain metastasis frequently occurs in individuals with cancer and is often fatal. We used multiphoton laser scanning microscopy to image the single steps of metastasis formation in real time. Thus, it was possible to track the fate of individual metastasizing cancer cells in vivo in relation to blood vessels deep in the mouse brain over minutes to months. The essential steps in this model were arrest at vascular branch points, early extravasation, persistent close contacts to microvessels and perivascular growth by vessel cooption (melanoma) or early angiogenesis (lung cancer). Inefficient steps differed between the tumor types. Long-term dormancy was only observed for single perivascular cancer cells, some of which moved continuously. Vascular endothelial growth factor-A (VEGF-A) inhibition induced long-term dormancy of lung cancer micrometastases by preventing angiogenic growth to macrometastases. The ability to image the establishment of brain metastases in vivo provides new insights into their evolution and response to therapies.