瑞士联邦理工学院(ETH)苏黎世分校Nicola Aceto团队近期取得重要工作进展，他们研究发现睡眠过程中乳腺癌的转移性扩散会加速。这一研究成果2022年6月22日在线发表于《自然》杂志上。
研究人员观察到乳腺癌患者和小鼠模型中循环肿瘤细胞（CTC） 生成动态的惊人模式，强调大多数自发CTC血管内事件发生在睡眠期间。此外，他们证明了静息期的CTC非常容易转移，而在活动期产生的CTC缺乏转移能力。从机制上讲，CTCs的单细胞RNA测序分析显示，在患者和小鼠模型的休息阶段，有丝分裂基因显著上调，从而使转移能力得以提高。
研究人员发现褪黑激素、睾酮和糖皮质激素等关键的昼夜节律激素决定了CTC的生成动态，因此，胰岛素直接促进体内肿瘤细胞增殖，因此，具有高度转移倾向的CTCs的自发生成并不是连续发生的，而是集中在受影响个体的休息阶段，为合理的时间控制和治疗易转移的癌症提供了新的理论基础。
据介绍，肿瘤的转移扩散是通过CTC的造血细胞传播实现的。然而，一般来说，决定具有转移能力的CTCs产生的时间动态在很大程度上还不明确，人们通常认为CTCs不断地从生长中的肿瘤中脱落，或者是由于机械损伤而脱落。
附：英文原文
Title: The metastatic spread of breast cancer accelerates during sleep
Author: Diamantopoulou, Zoi, Castro-Giner, Francesc, Schwab, Fabienne Dominique, Foerster, Christiane, Saini, Massimo, Budinjas, Selina, Strittmatter, Karin, Krol, Ilona, Seifert, Bettina, Heinzelmann-Schwarz, Viola, Kurzeder, Christian, Rochlitz, Christoph, Vetter, Marcus, Weber, Walter Paul, Aceto, Nicola
Issue&Volume: 2022-06-22
Abstract: The metastatic spread of cancer is achieved by the haematogenous dissemination of circulating tumour cells (CTCs). Generally, however, the temporal dynamics that dictate the generation of metastasis-competent CTCs are largely uncharacterized, and it is often assumed that CTCs are constantly shed from growing tumours or are shed as a consequence of mechanical insults1. Here we observe a striking and unexpected pattern of CTC generation dynamics in both patients with breast cancer and mouse models, highlighting that most spontaneous CTC intravasation events occur during sleep. Further, we demonstrate that rest-phase CTCs are highly prone to metastasize, whereas CTCs generated during the active phase are devoid of metastatic ability. Mechanistically, single-cell RNA sequencing analysis of CTCs reveals a marked upregulation of mitotic genes exclusively during the rest phase in both patients and mouse models, enabling metastasis proficiency. Systemically, we find that key circadian rhythm hormones such as melatonin, testosterone and glucocorticoids dictate CTC generation dynamics, and as a consequence, that insulin directly promotes tumour cell proliferation in vivo, yet in a time-dependent manner. Thus, the spontaneous generation of CTCs with a high proclivity to metastasize does not occur continuously, but it is concentrated within the rest phase of the affected individual, providing a new rationale for time-controlled interrogation and treatment of metastasis-prone cancers.
DOI: 10.1038/s41586-022-04875-y
Source: https://www.nature.com/articles/s41586-022-04875-y
Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html
本期文章：《自然》：Online/在线发表
