Inserm, U935, Université Paris Sud, Villejuif, France.
Université Paris Sud, Université Paris Saclay, UFR de Médecine Kremlin Bicêtre, Le Kremlin-Bicêtre, France.
Nat Commun. 2020 Jun 24;11(1):3193. doi: 10.1038/s41467-020-16890-6.
Breast cancer is the most common type of cancer worldwide and one of the major causes of cancer death in women. Epidemiological studies have established a link between night-shift work and increased cancer risk, suggesting that circadian disruption may play a role in carcinogenesis. Here, we aim to shed light on the effect of chronic jetlag (JL) on mammary tumour development. To do this, we use a mouse model of spontaneous mammary tumourigenesis and subject it to chronic circadian disruption. We observe that circadian disruption significantly increases cancer-cell dissemination and lung metastasis. It also enhances the stemness and tumour-initiating potential of tumour cells and creates an immunosuppressive shift in the tumour microenvironment. Finally, our results suggest that the use of a CXCR2 inhibitor could correct the effect of JL on cancer-cell dissemination and metastasis. Altogether, our data provide a conceptual framework to better understand and manage the effects of chronic circadian disruption on breast cancer progression.
乳腺癌是全球最常见的癌症类型，也是女性癌症死亡的主要原因之一。流行病学研究已经证实，轮班工作与癌症风险增加之间存在关联，这表明昼夜节律紊乱可能在癌症发生中起作用。在这里，我们旨在阐明慢性时差（JL）对乳腺肿瘤发展的影响。为此，我们使用自发乳腺肿瘤发生的小鼠模型，并对其进行慢性昼夜节律破坏。我们观察到昼夜节律破坏显著增加了癌细胞的扩散和肺转移。它还增强了肿瘤细胞的干性和肿瘤起始能力，并在肿瘤微环境中产生免疫抑制性转变。最后，我们的结果表明，使用 CXCR2 抑制剂可以纠正 JL 对癌细胞扩散和转移的影响。总的来说，我们的数据提供了一个概念框架，以更好地理解和管理慢性昼夜节律破坏对乳腺癌进展的影响。
