文章目录

星形细胞层粘连蛋白211驱动脑内弥散性乳腺肿瘤细胞休眠

原文发布日期：2021-12-24

英文摘要：

摘要翻译：

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文章：

星形细胞层粘连蛋白211驱动脑内弥散性乳腺肿瘤细胞休眠

Astrocytic laminin-211 drives disseminated breast tumor cell dormancy in brain

原文发布日期：2021-12-24

英文摘要：

Although dormancy is thought to play a key role in the metastasis of breast tumor cells to the brain, our knowledge of the molecular mechanisms regulating disseminated tumor cell (DTC) dormancy in this organ is limited. Here using serial intravital imaging of dormant and metastatic triple-negative breast cancer lines, we identify escape from the single-cell or micrometastatic state as the rate-limiting step towards brain metastasis. We show that every DTC occupies a vascular niche, with quiescent DTCs residing on astrocyte endfeet. At these sites, astrocyte-deposited laminin-211 drives DTC quiescence by inducing the dystroglycan receptor to associate with yes-associated protein, thereby sequestering it from the nucleus and preventing its prometastatic functions. These findings identify a brain-specific mechanism of DTC dormancy and highlight the need for a more thorough understanding of tumor dormancy to develop therapeutic approaches that prevent brain metastasis.

摘要翻译：

尽管乳腺癌细胞向大脑转移时被认为与睡眠机制密切相关，但目前关于散转移癌细胞（DTC）向脑转移中调控其睡眠状态的分子机制的研究仍十分有限。在这里，我们使用体内活检序列对垂尼氏三阴性乳腺癌系进行长时间观察，发现癌细胞从单细胞或微转移状态逃逸是向大脑转移的关键步骤。我们发现，每一分散转移癌细胞占据一个血管间隙，静息状态的DTC位于神经元末梢上。这些位置上，神经元分泌的laminin-211促进了DTC的静息状态，通过使 dystroglycan 受体与 yes-associated protein 结合来实现这一功能，从而将yes相关蛋白从细胞核中隔离，阻止其促转移功能。这些发现明确了向大脑特异性的DTC睡眠机制，并突出了对肿瘤睡眠机制更深入的理解对于开发预防脑转移治疗方法的必要性。