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Mammary tissue-derived extracellular matrix hydrogels reveal the role of irradiation in driving a pro-tumor and immunosuppressive microenvironment
Radiation therapy (RT) is essential for triple negative breast cancer (TNBC) treatment. However, patients with TNBC continue to experience recurrence after RT. The role of the extracellular matrix (ECM) of irradiated breast tissue in tumor recurrence is still unknown. In this study, we evaluated the...
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Published in: | Biomaterials 2024-07, Vol.308, p.122531-122531, Article 122531 |
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creator | Zhu, Tian Alves, Steven M. Adamo, Arianna Wen, Xiaona Corn, Kevin C. Shostak, Anastasia Johnson, Shereena Shaub, Nicholas D. Martello, Shannon E. Hacker, Benjamin C. D'Amore, Antonio Bardhan, Rizia Rafat, Marjan |
description | Radiation therapy (RT) is essential for triple negative breast cancer (TNBC) treatment. However, patients with TNBC continue to experience recurrence after RT. The role of the extracellular matrix (ECM) of irradiated breast tissue in tumor recurrence is still unknown. In this study, we evaluated the structure, molecular composition, and mechanical properties of irradiated murine mammary fat pads (MFPs) and developed ECM hydrogels from decellularized tissues (dECM) to assess the effects of RT-induced ECM changes on breast cancer cell behavior. Irradiated MFPs were characterized by increased ECM deposition and fiber density compared to unirradiated controls, which may provide a platform for cell invasion and proliferation. ECM component changes in collagens I, IV, and VI, and fibronectin were observed following irradiation in both MFPs and dECM hydrogels. Encapsulated TNBC cell proliferation and invasive capacity was enhanced in irradiated dECM hydrogels. In addition, TNBC cells co-cultured with macrophages in irradiated dECM hydrogels induced M2 macrophage polarization and exhibited further increases in proliferation. Our study establishes that the ECM in radiation-damaged sites promotes TNBC invasion and proliferation as well as an immunosuppressive microenvironment. This work represents an important step toward elucidating how changes in the ECM after RT contribute to breast cancer recurrence. |
doi_str_mv | 10.1016/j.biomaterials.2024.122531 |
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However, patients with TNBC continue to experience recurrence after RT. The role of the extracellular matrix (ECM) of irradiated breast tissue in tumor recurrence is still unknown. In this study, we evaluated the structure, molecular composition, and mechanical properties of irradiated murine mammary fat pads (MFPs) and developed ECM hydrogels from decellularized tissues (dECM) to assess the effects of RT-induced ECM changes on breast cancer cell behavior. Irradiated MFPs were characterized by increased ECM deposition and fiber density compared to unirradiated controls, which may provide a platform for cell invasion and proliferation. ECM component changes in collagens I, IV, and VI, and fibronectin were observed following irradiation in both MFPs and dECM hydrogels. Encapsulated TNBC cell proliferation and invasive capacity was enhanced in irradiated dECM hydrogels. In addition, TNBC cells co-cultured with macrophages in irradiated dECM hydrogels induced M2 macrophage polarization and exhibited further increases in proliferation. Our study establishes that the ECM in radiation-damaged sites promotes TNBC invasion and proliferation as well as an immunosuppressive microenvironment. This work represents an important step toward elucidating how changes in the ECM after RT contribute to breast cancer recurrence.</description><identifier>ISSN: 0142-9612</identifier><identifier>ISSN: 1878-5905</identifier><identifier>EISSN: 1878-5905</identifier><identifier>DOI: 10.1016/j.biomaterials.2024.122531</identifier><identifier>PMID: 38531198</identifier><language>eng</language><publisher>Netherlands: Elsevier Ltd</publisher><subject>Animals ; Breast cancer ; Cell Line, Tumor ; Cell Proliferation - drug effects ; Cell Proliferation - radiation effects ; dECM hydrogels ; Extracellular Matrix - metabolism ; Female ; Humans ; Hydrogels - chemistry ; Invasion ; M2 macrophages ; Macrophages - metabolism ; Mammary Glands, Animal - radiation effects ; Mice ; Proliferation ; Radiation therapy ; Triple Negative Breast Neoplasms - pathology ; Triple Negative Breast Neoplasms - radiotherapy ; Tumor Microenvironment - radiation effects</subject><ispartof>Biomaterials, 2024-07, Vol.308, p.122531-122531, Article 122531</ispartof><rights>2024 The Authors</rights><rights>Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c431t-3175d1c24a65cbf63be9d6a4a165a633f7edee5d2f202353e9c358303ab7e3d43</cites><orcidid>0000-0003-0441-4393 ; 0000-0002-9471-4711 ; 0000-0002-2423-6451 ; 0000-0002-9444-4379 ; 0000-0002-6908-6071 ; 0000-0002-6892-4395 ; 0000-0003-1824-8007 ; 0000-0002-7825-9827 ; 0000-0001-7632-793X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38531198$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhu, Tian</creatorcontrib><creatorcontrib>Alves, Steven M.</creatorcontrib><creatorcontrib>Adamo, Arianna</creatorcontrib><creatorcontrib>Wen, Xiaona</creatorcontrib><creatorcontrib>Corn, Kevin C.</creatorcontrib><creatorcontrib>Shostak, Anastasia</creatorcontrib><creatorcontrib>Johnson, Shereena</creatorcontrib><creatorcontrib>Shaub, Nicholas D.</creatorcontrib><creatorcontrib>Martello, Shannon E.</creatorcontrib><creatorcontrib>Hacker, Benjamin C.</creatorcontrib><creatorcontrib>D'Amore, Antonio</creatorcontrib><creatorcontrib>Bardhan, Rizia</creatorcontrib><creatorcontrib>Rafat, Marjan</creatorcontrib><title>Mammary tissue-derived extracellular matrix hydrogels reveal the role of irradiation in driving a pro-tumor and immunosuppressive microenvironment</title><title>Biomaterials</title><addtitle>Biomaterials</addtitle><description>Radiation therapy (RT) is essential for triple negative breast cancer (TNBC) treatment. However, patients with TNBC continue to experience recurrence after RT. The role of the extracellular matrix (ECM) of irradiated breast tissue in tumor recurrence is still unknown. In this study, we evaluated the structure, molecular composition, and mechanical properties of irradiated murine mammary fat pads (MFPs) and developed ECM hydrogels from decellularized tissues (dECM) to assess the effects of RT-induced ECM changes on breast cancer cell behavior. Irradiated MFPs were characterized by increased ECM deposition and fiber density compared to unirradiated controls, which may provide a platform for cell invasion and proliferation. ECM component changes in collagens I, IV, and VI, and fibronectin were observed following irradiation in both MFPs and dECM hydrogels. Encapsulated TNBC cell proliferation and invasive capacity was enhanced in irradiated dECM hydrogels. In addition, TNBC cells co-cultured with macrophages in irradiated dECM hydrogels induced M2 macrophage polarization and exhibited further increases in proliferation. Our study establishes that the ECM in radiation-damaged sites promotes TNBC invasion and proliferation as well as an immunosuppressive microenvironment. This work represents an important step toward elucidating how changes in the ECM after RT contribute to breast cancer recurrence.</description><subject>Animals</subject><subject>Breast cancer</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation - drug effects</subject><subject>Cell Proliferation - radiation effects</subject><subject>dECM hydrogels</subject><subject>Extracellular Matrix - metabolism</subject><subject>Female</subject><subject>Humans</subject><subject>Hydrogels - chemistry</subject><subject>Invasion</subject><subject>M2 macrophages</subject><subject>Macrophages - metabolism</subject><subject>Mammary Glands, Animal - radiation effects</subject><subject>Mice</subject><subject>Proliferation</subject><subject>Radiation therapy</subject><subject>Triple Negative Breast Neoplasms - pathology</subject><subject>Triple Negative Breast Neoplasms - radiotherapy</subject><subject>Tumor Microenvironment - radiation effects</subject><issn>0142-9612</issn><issn>1878-5905</issn><issn>1878-5905</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><recordid>eNqNkc2OFCEUhYnROO3oKxjiyk21UBT148aY8TcZ40bXhIJb3XQKaC9UZeY1fGLp9DgZd64I4dxzuOcj5BVnW854--awHV30OgM6Padtzepmy-taCv6IbHjf9ZUcmHxMNow3dTW0vL4gz1I6sHJnTf2UXIi-iPnQb8jvb9p7jbc0u5QWqGwxXcFSuMmoDczzMmukJQzdDd3fWow7mBNFWEHPNO-BYpyBxok6RG2dzi4G6gK1xceFHdX0iLHKi49IdbDUeb-EmJbjESGlkkW9MxghrA5j8BDyc_JkKnvBi7vzkvz89PHH1Zfq-vvnr1fvryvTCJ4rwTtpuakb3UozTq0YYbCtbjRvpW6FmDqwANLWUylISAGDEbIXTOixA2EbcUnenX2Py-jBmhKNelZHdKdCVNRO_fsS3F7t4qo4Z62U3VAcXt85YPy1QMrKu3QqTQeIS1KCMdGUriUr0rdnadk1JYTpPoczdaKqDuohVXWiqs5Uy_DLhz-9H_2LsQg-nAWFDawOUCXjIBiwDsFkZaP7n5w_JYDAyA</recordid><startdate>20240701</startdate><enddate>20240701</enddate><creator>Zhu, Tian</creator><creator>Alves, Steven M.</creator><creator>Adamo, Arianna</creator><creator>Wen, Xiaona</creator><creator>Corn, Kevin C.</creator><creator>Shostak, Anastasia</creator><creator>Johnson, Shereena</creator><creator>Shaub, Nicholas D.</creator><creator>Martello, Shannon E.</creator><creator>Hacker, Benjamin C.</creator><creator>D'Amore, Antonio</creator><creator>Bardhan, Rizia</creator><creator>Rafat, Marjan</creator><general>Elsevier Ltd</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-0441-4393</orcidid><orcidid>https://orcid.org/0000-0002-9471-4711</orcidid><orcidid>https://orcid.org/0000-0002-2423-6451</orcidid><orcidid>https://orcid.org/0000-0002-9444-4379</orcidid><orcidid>https://orcid.org/0000-0002-6908-6071</orcidid><orcidid>https://orcid.org/0000-0002-6892-4395</orcidid><orcidid>https://orcid.org/0000-0003-1824-8007</orcidid><orcidid>https://orcid.org/0000-0002-7825-9827</orcidid><orcidid>https://orcid.org/0000-0001-7632-793X</orcidid></search><sort><creationdate>20240701</creationdate><title>Mammary tissue-derived extracellular matrix hydrogels reveal the role of irradiation in driving a pro-tumor and immunosuppressive microenvironment</title><author>Zhu, Tian ; 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However, patients with TNBC continue to experience recurrence after RT. The role of the extracellular matrix (ECM) of irradiated breast tissue in tumor recurrence is still unknown. In this study, we evaluated the structure, molecular composition, and mechanical properties of irradiated murine mammary fat pads (MFPs) and developed ECM hydrogels from decellularized tissues (dECM) to assess the effects of RT-induced ECM changes on breast cancer cell behavior. Irradiated MFPs were characterized by increased ECM deposition and fiber density compared to unirradiated controls, which may provide a platform for cell invasion and proliferation. ECM component changes in collagens I, IV, and VI, and fibronectin were observed following irradiation in both MFPs and dECM hydrogels. Encapsulated TNBC cell proliferation and invasive capacity was enhanced in irradiated dECM hydrogels. In addition, TNBC cells co-cultured with macrophages in irradiated dECM hydrogels induced M2 macrophage polarization and exhibited further increases in proliferation. Our study establishes that the ECM in radiation-damaged sites promotes TNBC invasion and proliferation as well as an immunosuppressive microenvironment. This work represents an important step toward elucidating how changes in the ECM after RT contribute to breast cancer recurrence.</abstract><cop>Netherlands</cop><pub>Elsevier Ltd</pub><pmid>38531198</pmid><doi>10.1016/j.biomaterials.2024.122531</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0003-0441-4393</orcidid><orcidid>https://orcid.org/0000-0002-9471-4711</orcidid><orcidid>https://orcid.org/0000-0002-2423-6451</orcidid><orcidid>https://orcid.org/0000-0002-9444-4379</orcidid><orcidid>https://orcid.org/0000-0002-6908-6071</orcidid><orcidid>https://orcid.org/0000-0002-6892-4395</orcidid><orcidid>https://orcid.org/0000-0003-1824-8007</orcidid><orcidid>https://orcid.org/0000-0002-7825-9827</orcidid><orcidid>https://orcid.org/0000-0001-7632-793X</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Animals Breast cancer Cell Line, Tumor Cell Proliferation - drug effects Cell Proliferation - radiation effects dECM hydrogels Extracellular Matrix - metabolism Female Humans Hydrogels - chemistry Invasion M2 macrophages Macrophages - metabolism Mammary Glands, Animal - radiation effects Mice Proliferation Radiation therapy Triple Negative Breast Neoplasms - pathology Triple Negative Breast Neoplasms - radiotherapy Tumor Microenvironment - radiation effects |
title | Mammary tissue-derived extracellular matrix hydrogels reveal the role of irradiation in driving a pro-tumor and immunosuppressive microenvironment |
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