The EACR’s ‘Highlights in Cancer Research’ is a regular summary of the most interesting and impactful recent papers in cancer research, curated by the Board of the European Association for Cancer Research (EACR).
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He, X.Y. et al. Cancer Cell 42(3), 474-486.E12 (2024).
doi: 10.1016/j.ccell.2024.01.013.
Summary of the findings
Summary of the findingsChronic stress increases the likelihood of cancer patients developing metastasis (i.e., the spread of cancer to other parts of the body) and reduces the chances of survival, though the exact reasons remain unclear. This study investigated how chronic stress impacts metastasis, and identified stress-induced changes in the microenvironment mediated by neutrophils as a key mechanism.
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Using mouse models, a 2- to 4-fold increase in metastasis to the lungs or spleen was observed when mice were exposed to chronic stress. Chronic stress altered the lung microenvironment, with the accumulation of the extracellular matrix protein fibronectin and reduced T cell infiltration. Chronic stress majorly affected neutrophils: increasing their lung infiltration, disrupting their normal circadian rhythms, and inducing neutrophil extracellular trap (NET) formation. Mice with neutrophils that lacked the classical receptor for the glucocorticoid stress hormone did not produce NETs nor displayed increased metastasis after chronic stress exposure. Additionally, digesting the NETs with an enzyme called DNase I, prevented the metastasis caused by chronic stress.
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In conclusion, glucocorticoid release during chronic stress prompts NET formation, establishing an environment that fosters spread of cancer. Targeting NETs could potentially prevent metastasis recurrence in cancer patients experiencing chronic stress.
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Future impact
Understanding the impact of chronic stress on metastasis and the specific roles of neutrophils in driving stress-associated metastasis can inform the development of strategies to prevent or manage the metastatic spread of cancer cells. The development of drugs to inhibit NET formation could potentially benefit patients at risk of metastasis, as such drugs may slow or stop the spread of cancer.
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Together, the findings of the study provide valuable insights into the relationship between stress, the immune system, and cancer progression. It highlights the importance of managing stress in cancer treatment and prevention.
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