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)
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