Exosomes Derived from Radioresistant Breast Cancer Cells Promote Therapeutic Resistance in Naïve Recipient Cells

Radiation resistance is a significant challenge in the treatment of breast cancer in humans. Human breast cancer is commonly treated with surgery and adjuvant chemotherapy/radiotherapy, but recurrence and metastasis upon the development of therapy resistance results in treatment failure. Exosomes ar...

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Autores principales: Payton, Chantell, Pang, Lisa Y., Gray, Mark, Argyle, David J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8704086/
https://www.ncbi.nlm.nih.gov/pubmed/34945782
http://dx.doi.org/10.3390/jpm11121310
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author Payton, Chantell
Pang, Lisa Y.
Gray, Mark
Argyle, David J.
author_facet Payton, Chantell
Pang, Lisa Y.
Gray, Mark
Argyle, David J.
author_sort Payton, Chantell
collection PubMed
description Radiation resistance is a significant challenge in the treatment of breast cancer in humans. Human breast cancer is commonly treated with surgery and adjuvant chemotherapy/radiotherapy, but recurrence and metastasis upon the development of therapy resistance results in treatment failure. Exosomes are extracellular vesicles secreted by most cell types and contain biologically active cargo that, when transferred to recipient cells, can influence the cells’ genome and proteome. We propose that exosomes secreted by radioresistant (RR) cells may be able to disseminate the RR phenotype throughout the tumour. Here, we isolated exosomes from the human breast cancer cell line, MDA-MB-231, and the canine mammary carcinoma cell line, REM134, and their RR counterparts to investigate the effects of exosomes derived from RR cells on non-RR recipient cells. Canine mammary cancer cells lines have previously been shown to be excellent translational models of human breast cancer. This is consistent with our current data showing that exosomes derived from RR cells can increase cell viability and colony formation in naïve recipient cells and increase chemotherapy and radiotherapy resistance, in both species. These results are consistent in cancer stem cell and non-cancer stem cell populations. Significantly, exosomes derived from RR cells increased the tumoursphere-forming ability of recipient cells compared to exosomes derived from non-RR cells. Our results show that exosomes are potential mediators of radiation resistance that could be therapeutically targeted.
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spelling pubmed-87040862021-12-25 Exosomes Derived from Radioresistant Breast Cancer Cells Promote Therapeutic Resistance in Naïve Recipient Cells Payton, Chantell Pang, Lisa Y. Gray, Mark Argyle, David J. J Pers Med Article Radiation resistance is a significant challenge in the treatment of breast cancer in humans. Human breast cancer is commonly treated with surgery and adjuvant chemotherapy/radiotherapy, but recurrence and metastasis upon the development of therapy resistance results in treatment failure. Exosomes are extracellular vesicles secreted by most cell types and contain biologically active cargo that, when transferred to recipient cells, can influence the cells’ genome and proteome. We propose that exosomes secreted by radioresistant (RR) cells may be able to disseminate the RR phenotype throughout the tumour. Here, we isolated exosomes from the human breast cancer cell line, MDA-MB-231, and the canine mammary carcinoma cell line, REM134, and their RR counterparts to investigate the effects of exosomes derived from RR cells on non-RR recipient cells. Canine mammary cancer cells lines have previously been shown to be excellent translational models of human breast cancer. This is consistent with our current data showing that exosomes derived from RR cells can increase cell viability and colony formation in naïve recipient cells and increase chemotherapy and radiotherapy resistance, in both species. These results are consistent in cancer stem cell and non-cancer stem cell populations. Significantly, exosomes derived from RR cells increased the tumoursphere-forming ability of recipient cells compared to exosomes derived from non-RR cells. Our results show that exosomes are potential mediators of radiation resistance that could be therapeutically targeted. MDPI 2021-12-06 /pmc/articles/PMC8704086/ /pubmed/34945782 http://dx.doi.org/10.3390/jpm11121310 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Payton, Chantell
Pang, Lisa Y.
Gray, Mark
Argyle, David J.
Exosomes Derived from Radioresistant Breast Cancer Cells Promote Therapeutic Resistance in Naïve Recipient Cells
title Exosomes Derived from Radioresistant Breast Cancer Cells Promote Therapeutic Resistance in Naïve Recipient Cells
title_full Exosomes Derived from Radioresistant Breast Cancer Cells Promote Therapeutic Resistance in Naïve Recipient Cells
title_fullStr Exosomes Derived from Radioresistant Breast Cancer Cells Promote Therapeutic Resistance in Naïve Recipient Cells
title_full_unstemmed Exosomes Derived from Radioresistant Breast Cancer Cells Promote Therapeutic Resistance in Naïve Recipient Cells
title_short Exosomes Derived from Radioresistant Breast Cancer Cells Promote Therapeutic Resistance in Naïve Recipient Cells
title_sort exosomes derived from radioresistant breast cancer cells promote therapeutic resistance in naïve recipient cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8704086/
https://www.ncbi.nlm.nih.gov/pubmed/34945782
http://dx.doi.org/10.3390/jpm11121310
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