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Comparative Analysis of the Development of Acquired Radioresistance in Canine and Human Mammary Cancer Cell Lines

Research using in vitro canine mammary cancer cell lines and naturally-occurring canine mammary tumors are not only fundamental models used to advance the understanding of cancer in veterinary patients, but are also regarded as excellent translational models of human breast cancer. Human breast canc...

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Autores principales: Gray, Mark, Turnbull, Arran K., Meehan, James, Martínez-Pérez, Carlos, Kay, Charlene, Pang, Lisa Y., Argyle, David J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7396503/
https://www.ncbi.nlm.nih.gov/pubmed/32851022
http://dx.doi.org/10.3389/fvets.2020.00439
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author Gray, Mark
Turnbull, Arran K.
Meehan, James
Martínez-Pérez, Carlos
Kay, Charlene
Pang, Lisa Y.
Argyle, David J.
author_facet Gray, Mark
Turnbull, Arran K.
Meehan, James
Martínez-Pérez, Carlos
Kay, Charlene
Pang, Lisa Y.
Argyle, David J.
author_sort Gray, Mark
collection PubMed
description Research using in vitro canine mammary cancer cell lines and naturally-occurring canine mammary tumors are not only fundamental models used to advance the understanding of cancer in veterinary patients, but are also regarded as excellent translational models of human breast cancer. Human breast cancer is commonly treated with radiotherapy; however, tumor response depends on both innate radiosensitivity and on tumor repopulation by cells that develop radioresistance. Comparative canine and human studies investigating the mechanisms of radioresistance may lead to novel cancer treatments that benefit both species. In this study, we developed a canine mammary cancer (REM-134) radioresistant (RR) cell line and investigated the cellular mechanisms related to the development of acquired radioresistance. We performed a comparative analysis of this resistant model with our previously developed human breast cancer radioresistant cell lines (MCF-7 RR, ZR-751 RR, and MDA-MB-231 RR), characterizing inherent differences through genetic, molecular, and cell biology approaches. RR cells demonstrated enhanced invasion/migration capabilities, with phenotypic evidence suggestive of epithelial-to-mesenchymal transition. Similarities were identified between the REM-134 RR, MCF-7 RR, and ZR-751 RR cell lines in relation to the pattern of expression of both epithelial and mesenchymal genes, in addition to WNT, PI3K, and MAPK pathway activation. Following the development of radioresistance, transcriptomic data indicated that parental MCF-7 and ZR-751 cell lines changed from a luminal A classification to basal/HER2-overexpressing (MCF-7 RR) and normal-like/HER2-overexpressing (ZR-751 RR). These radioresistant subtypes were similar to the REM-134 and REM-134 RR cell lines, which were classified as HER2-overexpressing. To our knowledge, our study is the first to generate a canine mammary cancer RR cell line model and provide a comparative genetic and phenotypic analysis of the mechanisms of acquired radioresistance between canine and human cancer cell lines. We demonstrate that the cellular processes that occur with the development of acquired radioresistance are similar between the human and canine cell lines; our results therefore suggest that the canine model is appropriate to study both human and canine radioresistant mammary cancers, and that treatment strategies used in human medicine may also be applicable to veterinary patients.
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spelling pubmed-73965032020-08-25 Comparative Analysis of the Development of Acquired Radioresistance in Canine and Human Mammary Cancer Cell Lines Gray, Mark Turnbull, Arran K. Meehan, James Martínez-Pérez, Carlos Kay, Charlene Pang, Lisa Y. Argyle, David J. Front Vet Sci Veterinary Science Research using in vitro canine mammary cancer cell lines and naturally-occurring canine mammary tumors are not only fundamental models used to advance the understanding of cancer in veterinary patients, but are also regarded as excellent translational models of human breast cancer. Human breast cancer is commonly treated with radiotherapy; however, tumor response depends on both innate radiosensitivity and on tumor repopulation by cells that develop radioresistance. Comparative canine and human studies investigating the mechanisms of radioresistance may lead to novel cancer treatments that benefit both species. In this study, we developed a canine mammary cancer (REM-134) radioresistant (RR) cell line and investigated the cellular mechanisms related to the development of acquired radioresistance. We performed a comparative analysis of this resistant model with our previously developed human breast cancer radioresistant cell lines (MCF-7 RR, ZR-751 RR, and MDA-MB-231 RR), characterizing inherent differences through genetic, molecular, and cell biology approaches. RR cells demonstrated enhanced invasion/migration capabilities, with phenotypic evidence suggestive of epithelial-to-mesenchymal transition. Similarities were identified between the REM-134 RR, MCF-7 RR, and ZR-751 RR cell lines in relation to the pattern of expression of both epithelial and mesenchymal genes, in addition to WNT, PI3K, and MAPK pathway activation. Following the development of radioresistance, transcriptomic data indicated that parental MCF-7 and ZR-751 cell lines changed from a luminal A classification to basal/HER2-overexpressing (MCF-7 RR) and normal-like/HER2-overexpressing (ZR-751 RR). These radioresistant subtypes were similar to the REM-134 and REM-134 RR cell lines, which were classified as HER2-overexpressing. To our knowledge, our study is the first to generate a canine mammary cancer RR cell line model and provide a comparative genetic and phenotypic analysis of the mechanisms of acquired radioresistance between canine and human cancer cell lines. We demonstrate that the cellular processes that occur with the development of acquired radioresistance are similar between the human and canine cell lines; our results therefore suggest that the canine model is appropriate to study both human and canine radioresistant mammary cancers, and that treatment strategies used in human medicine may also be applicable to veterinary patients. Frontiers Media S.A. 2020-07-23 /pmc/articles/PMC7396503/ /pubmed/32851022 http://dx.doi.org/10.3389/fvets.2020.00439 Text en Copyright © 2020 Gray, Turnbull, Meehan, Martínez-Pérez, Kay, Pang and Argyle. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Veterinary Science
Gray, Mark
Turnbull, Arran K.
Meehan, James
Martínez-Pérez, Carlos
Kay, Charlene
Pang, Lisa Y.
Argyle, David J.
Comparative Analysis of the Development of Acquired Radioresistance in Canine and Human Mammary Cancer Cell Lines
title Comparative Analysis of the Development of Acquired Radioresistance in Canine and Human Mammary Cancer Cell Lines
title_full Comparative Analysis of the Development of Acquired Radioresistance in Canine and Human Mammary Cancer Cell Lines
title_fullStr Comparative Analysis of the Development of Acquired Radioresistance in Canine and Human Mammary Cancer Cell Lines
title_full_unstemmed Comparative Analysis of the Development of Acquired Radioresistance in Canine and Human Mammary Cancer Cell Lines
title_short Comparative Analysis of the Development of Acquired Radioresistance in Canine and Human Mammary Cancer Cell Lines
title_sort comparative analysis of the development of acquired radioresistance in canine and human mammary cancer cell lines
topic Veterinary Science
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7396503/
https://www.ncbi.nlm.nih.gov/pubmed/32851022
http://dx.doi.org/10.3389/fvets.2020.00439
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