A synthetic metastatic niche reveals antitumor neutrophils drive breast cancer metastatic dormancy in the lungs
Abstract Biomaterial scaffolds mimicking the environment in metastatic organs can deconstruct complex signals and facilitate the study of cancer progression and metastasis. Here we report that a subcutaneous scaffold implant in mouse models of metastatic breast cancer in female mice recruits lung-tr...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-08-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-40478-5 |
| _version_ | 1797558082196209664 |
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| author | Jing Wang Ramon Ocadiz-Ruiz Matthew S. Hall Grace G. Bushnell Sophia M. Orbach Joseph T. Decker Ravi M. Raghani Yining Zhang Aaron H. Morris Jacqueline S. Jeruss Lonnie D. Shea |
| author_facet | Jing Wang Ramon Ocadiz-Ruiz Matthew S. Hall Grace G. Bushnell Sophia M. Orbach Joseph T. Decker Ravi M. Raghani Yining Zhang Aaron H. Morris Jacqueline S. Jeruss Lonnie D. Shea |
| author_sort | Jing Wang |
| collection | DOAJ |
| description | Abstract Biomaterial scaffolds mimicking the environment in metastatic organs can deconstruct complex signals and facilitate the study of cancer progression and metastasis. Here we report that a subcutaneous scaffold implant in mouse models of metastatic breast cancer in female mice recruits lung-tropic circulating tumor cells yet suppresses their growth through potent in situ antitumor immunity. In contrast, the lung, the endogenous metastatic organ for these models, develops lethal metastases in aggressive breast cancer, with less aggressive tumor models developing dormant lungs suppressing tumor growth. Our study reveals multifaceted roles of neutrophils in regulating metastasis. Breast cancer-educated neutrophils infiltrate the scaffold implants and lungs, secreting the same signal to attract lung-tropic circulating tumor cells. Second, antitumor and pro-tumor neutrophils are selectively recruited to the dormant scaffolds and lungs, respectively, responding to distinct groups of chemoattractants to establish activated or suppressive immune environments that direct different fates of cancer cells. |
| first_indexed | 2024-03-10T17:25:25Z |
| format | Article |
| id | doaj.art-7ceec19b147f4e66ae168caae2f3b2a2 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-10T17:25:25Z |
| publishDate | 2023-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-7ceec19b147f4e66ae168caae2f3b2a22023-11-20T10:11:38ZengNature PortfolioNature Communications2041-17232023-08-0114112010.1038/s41467-023-40478-5A synthetic metastatic niche reveals antitumor neutrophils drive breast cancer metastatic dormancy in the lungsJing Wang0Ramon Ocadiz-Ruiz1Matthew S. Hall2Grace G. Bushnell3Sophia M. Orbach4Joseph T. Decker5Ravi M. Raghani6Yining Zhang7Aaron H. Morris8Jacqueline S. Jeruss9Lonnie D. Shea10Department of Biomedical Engineering, University of MichiganDepartment of Biomedical Engineering, University of MichiganDepartment of Biomedical Engineering, University of MichiganDepartment of Biomedical Engineering, University of MichiganDepartment of Biomedical Engineering, University of MichiganDepartment of Biomedical Engineering, University of MichiganDepartment of Biomedical Engineering, University of MichiganDepartment of Chemical Engineering, University of MichiganDepartment of Biomedical Engineering, University of MichiganDepartment of Biomedical Engineering, University of MichiganDepartment of Biomedical Engineering, University of MichiganAbstract Biomaterial scaffolds mimicking the environment in metastatic organs can deconstruct complex signals and facilitate the study of cancer progression and metastasis. Here we report that a subcutaneous scaffold implant in mouse models of metastatic breast cancer in female mice recruits lung-tropic circulating tumor cells yet suppresses their growth through potent in situ antitumor immunity. In contrast, the lung, the endogenous metastatic organ for these models, develops lethal metastases in aggressive breast cancer, with less aggressive tumor models developing dormant lungs suppressing tumor growth. Our study reveals multifaceted roles of neutrophils in regulating metastasis. Breast cancer-educated neutrophils infiltrate the scaffold implants and lungs, secreting the same signal to attract lung-tropic circulating tumor cells. Second, antitumor and pro-tumor neutrophils are selectively recruited to the dormant scaffolds and lungs, respectively, responding to distinct groups of chemoattractants to establish activated or suppressive immune environments that direct different fates of cancer cells.https://doi.org/10.1038/s41467-023-40478-5 |
| spellingShingle | Jing Wang Ramon Ocadiz-Ruiz Matthew S. Hall Grace G. Bushnell Sophia M. Orbach Joseph T. Decker Ravi M. Raghani Yining Zhang Aaron H. Morris Jacqueline S. Jeruss Lonnie D. Shea A synthetic metastatic niche reveals antitumor neutrophils drive breast cancer metastatic dormancy in the lungs Nature Communications |
| title | A synthetic metastatic niche reveals antitumor neutrophils drive breast cancer metastatic dormancy in the lungs |
| title_full | A synthetic metastatic niche reveals antitumor neutrophils drive breast cancer metastatic dormancy in the lungs |
| title_fullStr | A synthetic metastatic niche reveals antitumor neutrophils drive breast cancer metastatic dormancy in the lungs |
| title_full_unstemmed | A synthetic metastatic niche reveals antitumor neutrophils drive breast cancer metastatic dormancy in the lungs |
| title_short | A synthetic metastatic niche reveals antitumor neutrophils drive breast cancer metastatic dormancy in the lungs |
| title_sort | synthetic metastatic niche reveals antitumor neutrophils drive breast cancer metastatic dormancy in the lungs |
| url | https://doi.org/10.1038/s41467-023-40478-5 |
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