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Exosomes from differentially activated macrophages influence dormancy or resurgence of breast cancer cells within bone marrow stroma

Breast cancer (BC) cells (BCCs) can retain cellular quiescence for decades, a phenomenon referred to as dormancy. BCCs show preference for the bone marrow (BM) where they can remain dormant for decades. Targeting BCCs within the BM is a challenge since the dormant BCCs reside within BM stroma, also...

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Autores principales: Walker, Nykia D., Elias, Michael, Guiro, Khadidiatou, Bhatia, Ranvir, Greco, Steven J., Bryan, Margarette, Gergues, Marina, Sandiford, Oleta A., Ponzio, Nicholas M., Leibovich, Samuel J., Rameshwar, Pranela
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6347644/
https://www.ncbi.nlm.nih.gov/pubmed/30683851
http://dx.doi.org/10.1038/s41419-019-1304-z
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author Walker, Nykia D.
Elias, Michael
Guiro, Khadidiatou
Bhatia, Ranvir
Greco, Steven J.
Bryan, Margarette
Gergues, Marina
Sandiford, Oleta A.
Ponzio, Nicholas M.
Leibovich, Samuel J.
Rameshwar, Pranela
author_facet Walker, Nykia D.
Elias, Michael
Guiro, Khadidiatou
Bhatia, Ranvir
Greco, Steven J.
Bryan, Margarette
Gergues, Marina
Sandiford, Oleta A.
Ponzio, Nicholas M.
Leibovich, Samuel J.
Rameshwar, Pranela
author_sort Walker, Nykia D.
collection PubMed
description Breast cancer (BC) cells (BCCs) can retain cellular quiescence for decades, a phenomenon referred to as dormancy. BCCs show preference for the bone marrow (BM) where they can remain dormant for decades. Targeting BCCs within the BM is a challenge since the dormant BCCs reside within BM stroma, also residence for hematopoietic stem cells (HSCs). Dormant BCCs could behave as cancer stem cells (CSCs). The CSCs and HSCs are similar by function and also, by commonly expressed genes. The method by which dormant BCCs transition into clinically metastatic cells remains unclear. This study tested the hypothesis that macrophages (MΦs) within BM stroma, facilitates dormancy or reverse this state into metastatic cells. MΦs exhibiting an M2 phenotype constitute ~10% of cultured BM stroma. The M2 MΦs form gap junctional intercellular communication (GJIC) with CSCs, resulting in cycling quiescence, reduced proliferation and carboplatin resistance. In contrast, MΦs expressing the M1 phenotype reversed BC dormancy. Activation of M2a MΦs via the toll-like receptor 4 (TLR4) switched to M1 phenotype. The switch can occur by direct activation of M2a MΦs, or indirectly through activation of mesenchymal stem cells. M1 MΦ-derived exosomes activated NFкB to reverse quiescent BCCs to cycling cells. Using an in vivo model of BC dormancy, injected Mi MOs sensitized BCCs to carboplatin and increased host survival. In summary, we have shown how BM stromal MΦs, through exosomes, regulate the behavior of BCCs, by either inducing or reversing dormancy.
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spelling pubmed-63476442019-01-28 Exosomes from differentially activated macrophages influence dormancy or resurgence of breast cancer cells within bone marrow stroma Walker, Nykia D. Elias, Michael Guiro, Khadidiatou Bhatia, Ranvir Greco, Steven J. Bryan, Margarette Gergues, Marina Sandiford, Oleta A. Ponzio, Nicholas M. Leibovich, Samuel J. Rameshwar, Pranela Cell Death Dis Article Breast cancer (BC) cells (BCCs) can retain cellular quiescence for decades, a phenomenon referred to as dormancy. BCCs show preference for the bone marrow (BM) where they can remain dormant for decades. Targeting BCCs within the BM is a challenge since the dormant BCCs reside within BM stroma, also residence for hematopoietic stem cells (HSCs). Dormant BCCs could behave as cancer stem cells (CSCs). The CSCs and HSCs are similar by function and also, by commonly expressed genes. The method by which dormant BCCs transition into clinically metastatic cells remains unclear. This study tested the hypothesis that macrophages (MΦs) within BM stroma, facilitates dormancy or reverse this state into metastatic cells. MΦs exhibiting an M2 phenotype constitute ~10% of cultured BM stroma. The M2 MΦs form gap junctional intercellular communication (GJIC) with CSCs, resulting in cycling quiescence, reduced proliferation and carboplatin resistance. In contrast, MΦs expressing the M1 phenotype reversed BC dormancy. Activation of M2a MΦs via the toll-like receptor 4 (TLR4) switched to M1 phenotype. The switch can occur by direct activation of M2a MΦs, or indirectly through activation of mesenchymal stem cells. M1 MΦ-derived exosomes activated NFкB to reverse quiescent BCCs to cycling cells. Using an in vivo model of BC dormancy, injected Mi MOs sensitized BCCs to carboplatin and increased host survival. In summary, we have shown how BM stromal MΦs, through exosomes, regulate the behavior of BCCs, by either inducing or reversing dormancy. Nature Publishing Group UK 2019-01-25 /pmc/articles/PMC6347644/ /pubmed/30683851 http://dx.doi.org/10.1038/s41419-019-1304-z Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Walker, Nykia D.
Elias, Michael
Guiro, Khadidiatou
Bhatia, Ranvir
Greco, Steven J.
Bryan, Margarette
Gergues, Marina
Sandiford, Oleta A.
Ponzio, Nicholas M.
Leibovich, Samuel J.
Rameshwar, Pranela
Exosomes from differentially activated macrophages influence dormancy or resurgence of breast cancer cells within bone marrow stroma
title Exosomes from differentially activated macrophages influence dormancy or resurgence of breast cancer cells within bone marrow stroma
title_full Exosomes from differentially activated macrophages influence dormancy or resurgence of breast cancer cells within bone marrow stroma
title_fullStr Exosomes from differentially activated macrophages influence dormancy or resurgence of breast cancer cells within bone marrow stroma
title_full_unstemmed Exosomes from differentially activated macrophages influence dormancy or resurgence of breast cancer cells within bone marrow stroma
title_short Exosomes from differentially activated macrophages influence dormancy or resurgence of breast cancer cells within bone marrow stroma
title_sort exosomes from differentially activated macrophages influence dormancy or resurgence of breast cancer cells within bone marrow stroma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6347644/
https://www.ncbi.nlm.nih.gov/pubmed/30683851
http://dx.doi.org/10.1038/s41419-019-1304-z
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