He, Xue-Yan, Gao, Yuan, Ng, David, Michalopoulou, Evdokia, George, Shanu, Adrover, Jose M, Sun, Lijuan, Albrengues, Jean, Dassler-Plenker, Juliane, Han, Xiao, Wan, Ledong, Wu, Xiaoli S, Shui, Longling S, Huang, Yu-Han, Liu, Bodu, Su, Chang, Spector, David L, Vakoc, Christopher R, VanAelst, Linda, Egeblad, Mikala (March 2024) Chronic stress causes metastasis via neutrophil-mediated changes to the microenvironment. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024, 2024 Apr 5-10, San Diego, CA.
Abstract
Chronic stress is associated with increased risk of metastasis and poor survival in cancer patients, yet the reasons are unclear. We show that chronic stress increased lung metastasis from disseminated cancer cells 2- to 4-fold in mice. Chronic stress significantly altered the lung microenvironment, with fibronectin accumulation, reduced T cell infiltration, and increased neutrophil infiltration. Depleting neutrophils abolished stress-induced metastasis, indicating their critical role. Chronic stress shifted neutrophils’ normal circadian rhythm, and, via glucocorticoid release, caused increased neutrophil extracellular trap (NET) formation. Importantly, in mice with neutrophil-specific glucocorticoid receptor deletion, chronic stress failed to increase NETs and metastasis. Furthermore, digesting NETs with deoxyribonuclease (DNase) I prevented chronic stress-induced metastasis. Together, our data show that glucocorticoids released during chronic stress cause NET formation and establish a metastasis-promoting microenvironment. Therefore, NETs could be targets for preventing metastatic recurrence in cancer patients, many of whom will experience chronic stress due to their disease.
| Item Type: | Conference or Workshop Item (Poster) |
|---|---|
| Subjects: | diseases & disorders > cancer diseases & disorders diseases & disorders > cancer > metastasis |
| CSHL Authors: | |
| Communities: | CSHL labs > Egeblad lab CSHL labs > Krainer lab CSHL labs > Meyer Lab CSHL labs > Spector lab CSHL labs > Vakoc lab CSHL labs > Van Aelst lab |
| SWORD Depositor: | CSHL Elements |
| Depositing User: | CSHL Elements |
| Date: | 22 March 2024 |
| Date Deposited: | 10 Sep 2024 12:30 |
| Last Modified: | 10 Sep 2024 12:30 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/41656 |
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