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Mesenchymal Stem Cell-Induced Doxorubicin Resistance in Triple Negative Breast Cancer
Triple negative breast cancer (TNBC) is an aggressive histological subtype with limited treatment options and a worse clinical outcome compared with other breast cancer subtypes. Doxorubicin is considered to be one of the most effective agents in the treatment of TNBC. Unfortunately, resistance to t...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi Publishing Corporation
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4124237/ https://www.ncbi.nlm.nih.gov/pubmed/25140317 http://dx.doi.org/10.1155/2014/532161 |
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author | Chen, Dar-Ren Lu, Dah-Yuu Lin, Hui-Yi Yeh, Wei-Lan |
author_facet | Chen, Dar-Ren Lu, Dah-Yuu Lin, Hui-Yi Yeh, Wei-Lan |
author_sort | Chen, Dar-Ren |
collection | PubMed |
description | Triple negative breast cancer (TNBC) is an aggressive histological subtype with limited treatment options and a worse clinical outcome compared with other breast cancer subtypes. Doxorubicin is considered to be one of the most effective agents in the treatment of TNBC. Unfortunately, resistance to this agent is common. In some drug-resistant cells, drug efflux is mediated by adenosine triphosphate-dependent membrane transporter termed adenosine triphosphate-binding cassette (ABC) transporter, which can drive the substrates across membranes against concentration gradient. In the tumor microenvironment, upon interaction with mesenchymal stem cells (MSCs), tumor cells exhibit altered biological functions of certain gene clusters, hence increasing stemness of tumor cells, migration ability, angiogenesis, and drug resistance. In our present study, we investigated the mechanism of TNBC drug resistance induced by adipose-derived MSCs. Upon exposure of TNBC to MSC-secreted conditioned medium (CM), noticeable drug resistance against doxorubicin with markedly increased BCRP protein expression was observed. Intracellular doxorubicin accumulation of TNBC was also decreased by MSC-secreted CM. Furthermore, we found that doxorubicin resistance of TNBC was mediated by IL-8 presented in the MSC-secreted CM. These findings may enrich the list of potential targets for overcoming drug resistance induced by MSCs in TNBC patients. |
format | Online Article Text |
id | pubmed-4124237 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Hindawi Publishing Corporation |
record_format | MEDLINE/PubMed |
spelling | pubmed-41242372014-08-19 Mesenchymal Stem Cell-Induced Doxorubicin Resistance in Triple Negative Breast Cancer Chen, Dar-Ren Lu, Dah-Yuu Lin, Hui-Yi Yeh, Wei-Lan Biomed Res Int Research Article Triple negative breast cancer (TNBC) is an aggressive histological subtype with limited treatment options and a worse clinical outcome compared with other breast cancer subtypes. Doxorubicin is considered to be one of the most effective agents in the treatment of TNBC. Unfortunately, resistance to this agent is common. In some drug-resistant cells, drug efflux is mediated by adenosine triphosphate-dependent membrane transporter termed adenosine triphosphate-binding cassette (ABC) transporter, which can drive the substrates across membranes against concentration gradient. In the tumor microenvironment, upon interaction with mesenchymal stem cells (MSCs), tumor cells exhibit altered biological functions of certain gene clusters, hence increasing stemness of tumor cells, migration ability, angiogenesis, and drug resistance. In our present study, we investigated the mechanism of TNBC drug resistance induced by adipose-derived MSCs. Upon exposure of TNBC to MSC-secreted conditioned medium (CM), noticeable drug resistance against doxorubicin with markedly increased BCRP protein expression was observed. Intracellular doxorubicin accumulation of TNBC was also decreased by MSC-secreted CM. Furthermore, we found that doxorubicin resistance of TNBC was mediated by IL-8 presented in the MSC-secreted CM. These findings may enrich the list of potential targets for overcoming drug resistance induced by MSCs in TNBC patients. Hindawi Publishing Corporation 2014 2014-07-16 /pmc/articles/PMC4124237/ /pubmed/25140317 http://dx.doi.org/10.1155/2014/532161 Text en Copyright © 2014 Dar-Ren Chen et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Chen, Dar-Ren Lu, Dah-Yuu Lin, Hui-Yi Yeh, Wei-Lan Mesenchymal Stem Cell-Induced Doxorubicin Resistance in Triple Negative Breast Cancer |
title | Mesenchymal Stem Cell-Induced Doxorubicin Resistance in Triple Negative Breast Cancer |
title_full | Mesenchymal Stem Cell-Induced Doxorubicin Resistance in Triple Negative Breast Cancer |
title_fullStr | Mesenchymal Stem Cell-Induced Doxorubicin Resistance in Triple Negative Breast Cancer |
title_full_unstemmed | Mesenchymal Stem Cell-Induced Doxorubicin Resistance in Triple Negative Breast Cancer |
title_short | Mesenchymal Stem Cell-Induced Doxorubicin Resistance in Triple Negative Breast Cancer |
title_sort | mesenchymal stem cell-induced doxorubicin resistance in triple negative breast cancer |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4124237/ https://www.ncbi.nlm.nih.gov/pubmed/25140317 http://dx.doi.org/10.1155/2014/532161 |
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