Chronic Stress‐Induced and Tumor Derived SP1+ Exosomes Polarizing IL‐1β+ Neutrophils to Increase Lung Metastasis of Breast Cancer
Abstract Chronic stress can significantly promote breast cancer progression. When exposed to chronic stress, exosomes released from neural and neuroendocrine cells in the central nervous system are enhanced and modified. However, whether tumor‐derived exosomes (TDEs) are influenced by chronic stress...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2025-01-01
|
| Series: | Advanced Science |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/advs.202310266 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832582736537190400 |
|---|---|
| author | Leyi Zhang Jun Pan Meijun Wang Jini Yang Sangsang Zhu Lili Li Xiaoxiao Hu Zhen Wang Liwei Pang Peng Li Fang Jia Guohong Ren Yi Zhang Danying Xu Fuming Qiu Jian Huang |
| author_facet | Leyi Zhang Jun Pan Meijun Wang Jini Yang Sangsang Zhu Lili Li Xiaoxiao Hu Zhen Wang Liwei Pang Peng Li Fang Jia Guohong Ren Yi Zhang Danying Xu Fuming Qiu Jian Huang |
| author_sort | Leyi Zhang |
| collection | DOAJ |
| description | Abstract Chronic stress can significantly promote breast cancer progression. When exposed to chronic stress, exosomes released from neural and neuroendocrine cells in the central nervous system are enhanced and modified. However, whether tumor‐derived exosomes (TDEs) are influenced by chronic stress and participate in chronic stress‐mediated 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 β receptor in 4T1 tumor‐bearing mice. Exosomes injection and blockade experiments indicate that exosomes play a crucial role in chronic stress‐mediated lung metastasis of breast cancer. Chronic stress‐induced 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‐1β by neutrophils through the activation of the TLR4‐NFκβ pathway, ultimately aggravating lung metastasis of breast cancer. Collectively, this study provides a novel mechanism by which neutrophils within a pre‐metastatic niche acquire their inflamed phenotype and establishes an important link among neuroendocrine changes, exosomes, immunity, and metastasis. |
| format | Article |
| id | doaj-art-292ae6637c7c46ba976f1c806d9d74e0 |
| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-292ae6637c7c46ba976f1c806d9d74e02025-01-29T09:50:18ZengWileyAdvanced Science2198-38442025-01-01124n/an/a10.1002/advs.202310266Chronic Stress‐Induced and Tumor Derived SP1+ Exosomes Polarizing IL‐1β+ Neutrophils to Increase Lung Metastasis of Breast CancerLeyi Zhang0Jun Pan1Meijun Wang2Jini Yang3Sangsang Zhu4Lili Li5Xiaoxiao Hu6Zhen Wang7Liwei Pang8Peng Li9Fang Jia10Guohong Ren11Yi Zhang12Danying Xu13Fuming Qiu14Jian Huang15Department of Breast Surgery Second Affiliated Hospital Zhejiang University School of Medicine 88 Jiefang Road Hangzhou Zhejiang 310009 ChinaDepartment of Breast Surgery Second Affiliated Hospital Zhejiang University School of Medicine 88 Jiefang Road Hangzhou Zhejiang 310009 ChinaKey Laboratory of Tumor Microenvironment and Immune Therapy of Zhejiang Province Second Affiliated Hospital Zhejiang University School of Medicine Hangzhou Zhejiang 310009 ChinaKey Laboratory of Tumor Microenvironment and Immune Therapy of Zhejiang Province Second Affiliated Hospital Zhejiang University School of Medicine Hangzhou Zhejiang 310009 ChinaKey Laboratory of Tumor Microenvironment and Immune Therapy of Zhejiang Province Second Affiliated Hospital Zhejiang University School of Medicine Hangzhou Zhejiang 310009 ChinaKey Laboratory of Tumor Microenvironment and Immune Therapy of Zhejiang Province Second Affiliated Hospital Zhejiang University School of Medicine Hangzhou Zhejiang 310009 ChinaKey Laboratory of Tumor Microenvironment and Immune Therapy of Zhejiang Province Second Affiliated Hospital Zhejiang University School of Medicine Hangzhou Zhejiang 310009 ChinaDepartment of Breast Surgery Second Affiliated Hospital Zhejiang University School of Medicine 88 Jiefang Road Hangzhou Zhejiang 310009 ChinaDepartment of Breast Surgery Second Affiliated Hospital Zhejiang University School of Medicine 88 Jiefang Road Hangzhou Zhejiang 310009 ChinaKey Laboratory of Tumor Microenvironment and Immune Therapy of Zhejiang Province Second Affiliated Hospital Zhejiang University School of Medicine Hangzhou Zhejiang 310009 ChinaKey Laboratory of Tumor Microenvironment and Immune Therapy of Zhejiang Province Second Affiliated Hospital Zhejiang University School of Medicine Hangzhou Zhejiang 310009 ChinaKey Laboratory of Tumor Microenvironment and Immune Therapy of Zhejiang Province Second Affiliated Hospital Zhejiang University School of Medicine Hangzhou Zhejiang 310009 ChinaDepartment of Breast Surgery Second Affiliated Hospital Zhejiang University School of Medicine 88 Jiefang Road Hangzhou Zhejiang 310009 ChinaDepartment of Breast Surgery Second Affiliated Hospital Zhejiang University School of Medicine 88 Jiefang Road Hangzhou Zhejiang 310009 ChinaKey Laboratory of Tumor Microenvironment and Immune Therapy of Zhejiang Province Second Affiliated Hospital Zhejiang University School of Medicine Hangzhou Zhejiang 310009 ChinaDepartment of Breast Surgery Second Affiliated Hospital Zhejiang University School of Medicine 88 Jiefang Road Hangzhou Zhejiang 310009 ChinaAbstract Chronic stress can significantly promote breast cancer progression. When exposed to chronic stress, exosomes released from neural and neuroendocrine cells in the central nervous system are enhanced and modified. However, whether tumor‐derived exosomes (TDEs) are influenced by chronic stress and participate in chronic stress‐mediated 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 β receptor in 4T1 tumor‐bearing mice. Exosomes injection and blockade experiments indicate that exosomes play a crucial role in chronic stress‐mediated lung metastasis of breast cancer. Chronic stress‐induced 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‐1β by neutrophils through the activation of the TLR4‐NFκβ pathway, ultimately aggravating lung metastasis of breast cancer. Collectively, this study provides a novel mechanism by which neutrophils within a pre‐metastatic niche acquire their inflamed phenotype and establishes an important link among neuroendocrine changes, exosomes, immunity, and metastasis.https://doi.org/10.1002/advs.202310266breast cancerchronic stressexosomeslung metastasisneutrophils |
| spellingShingle | Leyi Zhang Jun Pan Meijun Wang Jini Yang Sangsang Zhu Lili Li Xiaoxiao Hu Zhen Wang Liwei Pang Peng Li Fang Jia Guohong Ren Yi Zhang Danying Xu Fuming Qiu Jian Huang Chronic Stress‐Induced and Tumor Derived SP1+ Exosomes Polarizing IL‐1β+ Neutrophils to Increase Lung Metastasis of Breast Cancer Advanced Science breast cancer chronic stress exosomes lung metastasis neutrophils |
| title | Chronic Stress‐Induced and Tumor Derived SP1+ Exosomes Polarizing IL‐1β+ Neutrophils to Increase Lung Metastasis of Breast Cancer |
| title_full | Chronic Stress‐Induced and Tumor Derived SP1+ Exosomes Polarizing IL‐1β+ Neutrophils to Increase Lung Metastasis of Breast Cancer |
| title_fullStr | Chronic Stress‐Induced and Tumor Derived SP1+ Exosomes Polarizing IL‐1β+ Neutrophils to Increase Lung Metastasis of Breast Cancer |
| title_full_unstemmed | Chronic Stress‐Induced and Tumor Derived SP1+ Exosomes Polarizing IL‐1β+ Neutrophils to Increase Lung Metastasis of Breast Cancer |
| title_short | Chronic Stress‐Induced and Tumor Derived SP1+ Exosomes Polarizing IL‐1β+ Neutrophils to Increase Lung Metastasis of Breast Cancer |
| title_sort | chronic stress induced and tumor derived sp1 exosomes polarizing il 1β neutrophils to increase lung metastasis of breast cancer |
| topic | breast cancer chronic stress exosomes lung metastasis neutrophils |
| url | https://doi.org/10.1002/advs.202310266 |
| work_keys_str_mv | AT leyizhang chronicstressinducedandtumorderivedsp1exosomespolarizingil1bneutrophilstoincreaselungmetastasisofbreastcancer AT junpan chronicstressinducedandtumorderivedsp1exosomespolarizingil1bneutrophilstoincreaselungmetastasisofbreastcancer AT meijunwang chronicstressinducedandtumorderivedsp1exosomespolarizingil1bneutrophilstoincreaselungmetastasisofbreastcancer AT jiniyang chronicstressinducedandtumorderivedsp1exosomespolarizingil1bneutrophilstoincreaselungmetastasisofbreastcancer AT sangsangzhu chronicstressinducedandtumorderivedsp1exosomespolarizingil1bneutrophilstoincreaselungmetastasisofbreastcancer AT lilili chronicstressinducedandtumorderivedsp1exosomespolarizingil1bneutrophilstoincreaselungmetastasisofbreastcancer AT xiaoxiaohu chronicstressinducedandtumorderivedsp1exosomespolarizingil1bneutrophilstoincreaselungmetastasisofbreastcancer AT zhenwang chronicstressinducedandtumorderivedsp1exosomespolarizingil1bneutrophilstoincreaselungmetastasisofbreastcancer AT liweipang chronicstressinducedandtumorderivedsp1exosomespolarizingil1bneutrophilstoincreaselungmetastasisofbreastcancer AT pengli chronicstressinducedandtumorderivedsp1exosomespolarizingil1bneutrophilstoincreaselungmetastasisofbreastcancer AT fangjia chronicstressinducedandtumorderivedsp1exosomespolarizingil1bneutrophilstoincreaselungmetastasisofbreastcancer AT guohongren chronicstressinducedandtumorderivedsp1exosomespolarizingil1bneutrophilstoincreaselungmetastasisofbreastcancer AT yizhang chronicstressinducedandtumorderivedsp1exosomespolarizingil1bneutrophilstoincreaselungmetastasisofbreastcancer AT danyingxu chronicstressinducedandtumorderivedsp1exosomespolarizingil1bneutrophilstoincreaselungmetastasisofbreastcancer AT fumingqiu chronicstressinducedandtumorderivedsp1exosomespolarizingil1bneutrophilstoincreaselungmetastasisofbreastcancer AT jianhuang chronicstressinducedandtumorderivedsp1exosomespolarizingil1bneutrophilstoincreaselungmetastasisofbreastcancer |