文章目录

肺内皮利用易感肿瘤细胞状态指导转移潜伏

原文发布日期：2024-02-02

英文摘要：

摘要翻译：

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文章：

肺内皮利用易感肿瘤细胞状态指导转移潜伏

Lung endothelium exploits susceptible tumor cell states to instruct metastatic latency

原文发布日期：2024-02-02

英文摘要：

In metastasis, cancer cells travel around the circulation to colonize distant sites. Due to the rarity of these events, the immediate fates of metastasizing tumor cells (mTCs) are poorly understood while the role of the endothelium as a dissemination interface remains elusive. Using a newly developed combinatorial mTC enrichment approach, we provide a transcriptional blueprint of the early colonization process. Following their arrest at the metastatic site, mTCs were found to either proliferate intravascularly or extravasate, thereby establishing metastatic latency. Endothelial-derived angiocrine Wnt factors drive this bifurcation, instructing mTCs to follow the extravasation–latency route. Surprisingly, mTC responsiveness towards niche-derived Wnt was established at the epigenetic level, which predetermined tumor cell behavior. Whereas hypomethylation enabled high Wnt activity leading to metastatic latency, methylated mTCs exhibited low activity and proliferated intravascularly. Collectively the data identify the predetermined methylation status of disseminated tumor cells as a key regulator of mTC behavior in the metastatic niche.

摘要翻译：

在转移过程中，癌细胞通过血液循环到达远处的部位。由于这些事件的罕见性，转移癌细胞（mTCs）的即时命运尚不清楚，而血管内皮细胞在扩散过程中所起的作用仍然不明朗。我们利用了一种新型组合富集方法，提供了早期殖民过程的转录图谱。在转移部位停止后，发现它们要么通过血管内进行增殖，要么进行移行。从而建立起了转移性间的歇斯底里。内皮细胞来源的角化素Wnt因素引导了这种分化，指导转移癌细胞遵循移行—歇斯底里路线。出乎意料的是，在表观遗传学水平上，转移癌细胞对微环境Wnt信号的反应性被建立下来，从而预设了肿瘤细胞的行为。而低甲基化促进了高Wnt活性导致转移性歇斯底里，而甲基化的mTC则活动低并进行血管内增殖。这些结果共同表明，离散肿瘤细胞的预设甲基化状态是转移性微环境中mTC行为的关键调节因素。