Extracellular vesicles from human breast cancer-resistant cells promote acquired drug resistance and pro-inflammatory macrophage response
IntroductionBreast cancer is a significant public health problem around the world, ranking first in deaths due to cancer in females. The therapy to fight breast cancer involves different methods, including conventional chemotherapy. However, the acquired resistance that tumors develop during the tre...
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Frontiers Media S.A.
2024-10-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1468229/full |
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| author | Patrick Santos Caroline P. Rezende Renan Piraine Bianca Oliveira Francielle B. Ferreira Vinicius S. Carvalho Rodrigo T. Calado Matteo Pellegrini Fausto Almeida |
| author_facet | Patrick Santos Caroline P. Rezende Renan Piraine Bianca Oliveira Francielle B. Ferreira Vinicius S. Carvalho Rodrigo T. Calado Matteo Pellegrini Fausto Almeida |
| author_sort | Patrick Santos |
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| description | IntroductionBreast cancer is a significant public health problem around the world, ranking first in deaths due to cancer in females. The therapy to fight breast cancer involves different methods, including conventional chemotherapy. However, the acquired resistance that tumors develop during the treatment is still a central cause of cancer-associated deaths. One mechanism that induces drug resistance is cell communication via extracellular vesicles (EVs), which can carry efflux transporters and miRNA that increase sensitive cells’ survivability to chemotherapy.MethodsOur study investigates the transcription changes modulated by EVs from tamoxifen- and doxorubicin-resistant breast cancer cells in sensitive cells and how these changes may induce acquired drug resistance, inhibit apoptosis, and increase survivability in the sensitive cells. Additionally, we exposed human macrophages to resistant EVs to understand the influence of EVs on immune responses.ResultsOur results suggest that the acquired drug resistance is associated with the ability of resistant EVs to upregulate several transporter classes, which are directly related to the increase of cell viability and survival of sensitive cells exposed to EVs before a low-dose drug treatment. In addition, we show evidence that resistant EVs may downregulate immune system factors to evade detection and block cell death by apoptosis in sensitive breast cancer cells. Our data also reveals that human macrophages in contact with resistant EVs trigger a pro-inflammatory cytokine secretion profile, an effect that may be helpful for future immunotherapy studies.DiscussionThese findings are the first transcriptome-wide analysis of cells exposed to resistant EVs, supporting that resistant EVs are associated with the acquired drug resistance process during chemotherapy by modulating different aspects of sensitive cancer cells that coffer the chemoresistance. |
| format | Article |
| id | doaj-art-9fe98e93046d4cd79ee572cf27a180c9 |
| institution | OA Journals |
| issn | 1664-3224 |
| language | English |
| publishDate | 2024-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-9fe98e93046d4cd79ee572cf27a180c92025-08-20T02:11:37ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-10-011510.3389/fimmu.2024.14682291468229Extracellular vesicles from human breast cancer-resistant cells promote acquired drug resistance and pro-inflammatory macrophage responsePatrick Santos0Caroline P. Rezende1Renan Piraine2Bianca Oliveira3Francielle B. Ferreira4Vinicius S. Carvalho5Rodrigo T. Calado6Matteo Pellegrini7Fausto Almeida8Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, BrazilDepartment of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, BrazilDepartment of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, BrazilDepartment of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, BrazilDepartment of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, BrazilDepartment of Medical Imaging, Hematology, and Oncology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, BrazilDepartment of Medical Imaging, Hematology, and Oncology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, BrazilDepartment of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, CA, United StatesDepartment of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, BrazilIntroductionBreast cancer is a significant public health problem around the world, ranking first in deaths due to cancer in females. The therapy to fight breast cancer involves different methods, including conventional chemotherapy. However, the acquired resistance that tumors develop during the treatment is still a central cause of cancer-associated deaths. One mechanism that induces drug resistance is cell communication via extracellular vesicles (EVs), which can carry efflux transporters and miRNA that increase sensitive cells’ survivability to chemotherapy.MethodsOur study investigates the transcription changes modulated by EVs from tamoxifen- and doxorubicin-resistant breast cancer cells in sensitive cells and how these changes may induce acquired drug resistance, inhibit apoptosis, and increase survivability in the sensitive cells. Additionally, we exposed human macrophages to resistant EVs to understand the influence of EVs on immune responses.ResultsOur results suggest that the acquired drug resistance is associated with the ability of resistant EVs to upregulate several transporter classes, which are directly related to the increase of cell viability and survival of sensitive cells exposed to EVs before a low-dose drug treatment. In addition, we show evidence that resistant EVs may downregulate immune system factors to evade detection and block cell death by apoptosis in sensitive breast cancer cells. Our data also reveals that human macrophages in contact with resistant EVs trigger a pro-inflammatory cytokine secretion profile, an effect that may be helpful for future immunotherapy studies.DiscussionThese findings are the first transcriptome-wide analysis of cells exposed to resistant EVs, supporting that resistant EVs are associated with the acquired drug resistance process during chemotherapy by modulating different aspects of sensitive cancer cells that coffer the chemoresistance.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1468229/fullchemoresistancetamoxifendoxorubicinimmunomodulationmembrane transporters |
| spellingShingle | Patrick Santos Caroline P. Rezende Renan Piraine Bianca Oliveira Francielle B. Ferreira Vinicius S. Carvalho Rodrigo T. Calado Matteo Pellegrini Fausto Almeida Extracellular vesicles from human breast cancer-resistant cells promote acquired drug resistance and pro-inflammatory macrophage response Frontiers in Immunology chemoresistance tamoxifen doxorubicin immunomodulation membrane transporters |
| title | Extracellular vesicles from human breast cancer-resistant cells promote acquired drug resistance and pro-inflammatory macrophage response |
| title_full | Extracellular vesicles from human breast cancer-resistant cells promote acquired drug resistance and pro-inflammatory macrophage response |
| title_fullStr | Extracellular vesicles from human breast cancer-resistant cells promote acquired drug resistance and pro-inflammatory macrophage response |
| title_full_unstemmed | Extracellular vesicles from human breast cancer-resistant cells promote acquired drug resistance and pro-inflammatory macrophage response |
| title_short | Extracellular vesicles from human breast cancer-resistant cells promote acquired drug resistance and pro-inflammatory macrophage response |
| title_sort | extracellular vesicles from human breast cancer resistant cells promote acquired drug resistance and pro inflammatory macrophage response |
| topic | chemoresistance tamoxifen doxorubicin immunomodulation membrane transporters |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1468229/full |
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