Department of Neurology, Ludwig-Maximilians University, Munich, Germany.
Nat Med. 2010 Jan;16(1):116-22. doi: 10.1038/nm.2072. Epub 2009 Dec 20.
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.
脑转移经常发生在癌症患者中，通常是致命的。我们使用多光子激光扫描显微镜实时成像转移形成的单个步骤。因此，有可能在数分钟到数月内追踪体内单个转移癌细胞在小鼠大脑深处血管内的命运。该模型中的关键步骤是在血管分支点处停滞、早期渗出、与微血管持续紧密接触以及通过血管选择（黑色素瘤）或早期血管生成（肺癌）进行血管周围生长。不同肿瘤类型的低效步骤不同。只有单个血管周围癌细胞长期休眠，其中一些细胞持续移动。血管内皮生长因子-A（VEGF-A）抑制通过阻止血管生成生长到巨转移来诱导肺癌微转移的长期休眠。体内成像脑转移建立的能力为其进化和对治疗的反应提供了新的见解。
