美国冷泉港实验室Mikala Egeblad小组发现，慢性压力通过中性粒细胞介导的微环境变化增加转移。相关论文于2024年2月22日在线发表在《癌细胞》杂志上。

研究人员表明，慢性应激会使小鼠肺部扩散癌细胞的转移增加2到4倍。慢性应激会明显改变肺部微环境，导致纤维粘连蛋白积聚、T细胞浸润减少和中性粒细胞浸润增加。消耗中性粒细胞可消除应激诱导的转移。慢性应激改变了中性粒细胞的正常昼夜节律，并通过释放糖皮质激素导致中性粒细胞胞外捕获物（NET）形成增加。在中性粒细胞特异性糖皮质激素受体缺失的小鼠中，慢性应激不会增加NET和转移。

此外，用DNA酶I消化NET可防止慢性应激诱导的转移。总之，这些数据表明，慢性应激时释放的糖皮质激素会导致NET的形成，并建立一个促进转移的微环境。因此，NET可以成为预防癌症患者转移性复发的靶点，因为许多癌症患者都会因疾病而经历慢性应激。

研究人员表示，慢性压力与癌症患者转移风险增加和生存率低有关，但原因尚不清楚。

附：英文原文

Title: Chronic stress increases metastasis via neutrophil-mediated changes to the microenvironment

Author: Xue-Yan He, Yuan Gao, David Ng, Evdokia Michalopoulou, Shanu George, Jose M. Adrover, Lijuan Sun, Jean Albrengues, Juliane Daler-Plenker, Xiao Han, Ledong Wan, Xiaoli Sky Wu, Longling S. Shui, Yu-Han Huang, Bodu Liu, Chang Su, David L. Spector, Christopher R. Vakoc, Linda Van Aelst, Mikala Egeblad

Issue&Volume: 2024-02-22

Abstract: Chronic stress is associated with increased risk of metastasis and poor survival incancer patients, yet the reasons are unclear. We show that chronic stress increaseslung metastasis from disseminated cancer cells 2- to 4-fold in mice. Chronic stresssignificantly alters the lung microenvironment, with fibronectin accumulation, reducedT cell infiltration, and increased neutrophil infiltration. Depleting neutrophilsabolishes stress-induced metastasis. Chronic stress shifts normal circadian rhythmof neutrophils and causes increased neutrophil extracellular trap (NET) formationvia glucocorticoid release. In mice with neutrophil-specific glucocorticoid receptordeletion, chronic stress fails to increase NETs and metastasis. Furthermore, digestingNETs with DNase I prevents chronic stress-induced metastasis. Together, our data showthat glucocorticoids released during chronic stress cause NET formation and establisha metastasis-promoting microenvironment. Therefore, NETs could be targets for preventingmetastatic recurrence in cancer patients, many of whom will experience chronic stressdue to their disease.

DOI: 10.1016/j.ccell.2024.01.013

Source: https://www.cell.com/cancer-cell/abstract/S1535-6108(24)00037-0