Chronic stress, a common issue in daily life, is particularly pronounced in patients with cancer. Chronic stress affects the whole body and perturbs systemic homeostasis, promoting cancer growth in mice. Whether and why chronic stress increases metastasis rates is still unknown. A study in Cancer Cell shows that chronic stress promotes metastasis in a metastatic lung cancer mouse model by increasing neutrophil responses. When analyzing the lung microenvironment, chronic stress induced a pro-metastatic environment increasing neutrophil infiltration. Further experiments revealed that stress altered the neutrophil circadian rhythm, with neutrophils peaking in number earlier and with an increase in neutrophil extracellular trap (NET) formation compared to control. Of note, this effect was not observed in adrenalectomized mice or glucocorticoid receptor-deleted mice. Additionally, decreasing neutrophil extracellular trap levels by using a digestive DNase I decreased metastasis rates. Altogether, these results show that chronic stress drives metastasis through the release of glucocorticoids, altering the microenvironment and triggering NET formation. These data show the importance of managing chronic stress in patients with cancer while hinting that modulating the lung microenvironment could decrease metastasis.

Original reference: He, X.Y. et al. Cancer Cell 42, 474-486.e12 (2024)

慢性压力是日常生活中的常见问题，在癌症患者中尤其明显。慢性压力会影响整个身体并扰乱全身稳态，促进小鼠癌症的生长。慢性压力是否以及为何会增加转移率仍不清楚。《癌细胞》中的一项研究表明，慢性应激通过增加中性粒细胞反应来促进转移性肺癌小鼠模型的转移。在分析肺部微环境时，慢性应激诱导了促转移环境，增加了中性粒细胞浸润。进一步的实验表明，与对照组相比，压力改变了中性粒细胞的昼夜节律，中性粒细胞数量更早达到峰值，并且中性粒细胞胞外陷阱（NET）形成增加。值得注意的是，在肾上腺切除的小鼠或糖皮质激素受体缺失的小鼠中没有观察到这种效应。此外，通过使用消化性 DNase I 降低中性粒细胞胞外陷阱水平可降低转移率。总而言之，这些结果表明，慢性应激通过释放糖皮质激素、改变微环境并触发 NET 形成来驱动转移。这些数据显示了控制癌症患者慢性压力的重要性，同时暗示调节肺部微环境可以减少转移。

原文参考： He, XY et al.癌细胞 42 , 474-486.e12 (2024)