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When exposed to chronic stress, exosomes released from neural and neuroendocrine cells in the central nervous system are enhanced and modified. However, whether tumor\u2010derived exosomes (TDEs) are influenced by chronic stress and participate in chronic stress\u2010mediated distant metastasis remains unclear. Here, it is shown that chronic stress remarkably facilitates the secretion of TDEs and modifies the contents of exosomes by activating the adrenergic \u03b2 receptor in 4T1 tumor\u2010bearing mice. Exosomes injection and blockade experiments indicate that exosomes play a crucial role in chronic stress\u2010mediated lung metastasis of breast cancer. Chronic stress\u2010induced TDEs are internalized by pulmonary neutrophils and strengthen neutrophil recruitment via the CXCL2 autocrine. In addition, the level of SP1 in TDEs increases, which favors the secretion of IL\u20101\u03b2 by neutrophils through the activation of the TLR4\u2010NF\u03ba\u03b2 pathway, ultimately aggravating lung metastasis of breast cancer. Collectively, this study provides a novel mechanism by which neutrophils within a pre\u2010metastatic niche acquire their inflamed phenotype and establishes an important link among neuroendocrine changes, exosomes, immunity, and metastasis.<\/jats:p>","DOI":"10.1002\/advs.202310266","type":"journal-article","created":{"date-parts":[[2024,12,4]],"date-time":"2024-12-04T10:12:09Z","timestamp":1733307129000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Chronic Stress\u2010Induced and Tumor Derived SP1\n                    <sup>+<\/sup>\n                    Exosomes Polarizing IL\u20101\u03b2\n                    <sup>+<\/sup>\n                    Neutrophils to Increase Lung Metastasis of Breast Cancer"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-0298-5119","authenticated-orcid":false,"given":"Leyi","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Breast Surgery Second Affiliated Hospital Zhejiang University School of Medicine  88 Jiefang Road Hangzhou Zhejiang 310009 China"},{"name":"Key Laboratory of Tumor Microenvironment and Immune Therapy of Zhejiang Province Second Affiliated Hospital Zhejiang University School of Medicine  Hangzhou Zhejiang 310009 China"},{"name":"Cancer Center Zhejiang University  Hangzhou Zhejiang 310009 China"},{"name":"Cancer Institute (Key Laboratory of Cancer Prevention &amp; 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