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Tumour cell-derived exosomes endow mesenchymal stromal cells with tumour-promotion capabilities

Mesenchymal stromal cells (MSCs) are a major component of the tumour microenvironment. A plethora of elegant studies focusing on tumour-derived MSCs have shown that they, unlike normal MSCs in other tissue, exhibit a strong ability to promote tumour progression. However, the mechanisms underlying th...

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Autores principales: Lin, L Y, Du, L M, Cao, K, Huang, Y, Yu, P F, Zhang, L Y, Li, F Y, Wang, Y, Shi, Y F
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5116561/
https://www.ncbi.nlm.nih.gov/pubmed/27132512
http://dx.doi.org/10.1038/onc.2016.131
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author Lin, L Y
Du, L M
Cao, K
Huang, Y
Yu, P F
Zhang, L Y
Li, F Y
Wang, Y
Shi, Y F
author_facet Lin, L Y
Du, L M
Cao, K
Huang, Y
Yu, P F
Zhang, L Y
Li, F Y
Wang, Y
Shi, Y F
author_sort Lin, L Y
collection PubMed
description Mesenchymal stromal cells (MSCs) are a major component of the tumour microenvironment. A plethora of elegant studies focusing on tumour-derived MSCs have shown that they, unlike normal MSCs in other tissue, exhibit a strong ability to promote tumour progression. However, the mechanisms underlying the conversion of normal MSCs into tumour-associated MSCs are unknown. We report here a critical role of tumour cell-derived exosomes in endowing bone marrow-derived MSCs (BM-MSCs) with a tumour-favourable phenotype. Tumour cell-derived exosomes affected neither the growth factor production nor the immunosuppressive property of MSCs; rather, they endowed MSCs with a strong ability to promote macrophage infiltration into B16-F0 melanoma or EL-4 lymphoma. Ablation of macrophages by clodronate liposome administration reversed the tumour-promoting effect of MSCs educated by tumour cell-derived exosomes (TE-MSCs) on the tumour growth. By comparing the chemokine profile of BM-MSCs with that of TE-MSCs, we found that TE-MSCs produced a large amount of CCR2 ligands, CCL2 and CCL7, which are responsible for macrophage recruitment. CCR2-specific inhibitor was found to block the tumour-promoting effect of TE-MSCs. Thus, our investigations demonstrated that tumour cell-derived exosomes confer BM-MSCs the ability to enhance tumour growth. Therefore, we uncovered a novel mechanism underlying the conversion of normal MSCs to tumour-associated MSCs.
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spelling pubmed-51165612016-12-16 Tumour cell-derived exosomes endow mesenchymal stromal cells with tumour-promotion capabilities Lin, L Y Du, L M Cao, K Huang, Y Yu, P F Zhang, L Y Li, F Y Wang, Y Shi, Y F Oncogene Short Communication Mesenchymal stromal cells (MSCs) are a major component of the tumour microenvironment. A plethora of elegant studies focusing on tumour-derived MSCs have shown that they, unlike normal MSCs in other tissue, exhibit a strong ability to promote tumour progression. However, the mechanisms underlying the conversion of normal MSCs into tumour-associated MSCs are unknown. We report here a critical role of tumour cell-derived exosomes in endowing bone marrow-derived MSCs (BM-MSCs) with a tumour-favourable phenotype. Tumour cell-derived exosomes affected neither the growth factor production nor the immunosuppressive property of MSCs; rather, they endowed MSCs with a strong ability to promote macrophage infiltration into B16-F0 melanoma or EL-4 lymphoma. Ablation of macrophages by clodronate liposome administration reversed the tumour-promoting effect of MSCs educated by tumour cell-derived exosomes (TE-MSCs) on the tumour growth. By comparing the chemokine profile of BM-MSCs with that of TE-MSCs, we found that TE-MSCs produced a large amount of CCR2 ligands, CCL2 and CCL7, which are responsible for macrophage recruitment. CCR2-specific inhibitor was found to block the tumour-promoting effect of TE-MSCs. Thus, our investigations demonstrated that tumour cell-derived exosomes confer BM-MSCs the ability to enhance tumour growth. Therefore, we uncovered a novel mechanism underlying the conversion of normal MSCs to tumour-associated MSCs. Nature Publishing Group 2016-11-17 2016-05-02 /pmc/articles/PMC5116561/ /pubmed/27132512 http://dx.doi.org/10.1038/onc.2016.131 Text en Copyright © 2016 Macmillan Publishers Limited http://creativecommons.org/licenses/by-nc-sa/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/4.0/
spellingShingle Short Communication
Lin, L Y
Du, L M
Cao, K
Huang, Y
Yu, P F
Zhang, L Y
Li, F Y
Wang, Y
Shi, Y F
Tumour cell-derived exosomes endow mesenchymal stromal cells with tumour-promotion capabilities
title Tumour cell-derived exosomes endow mesenchymal stromal cells with tumour-promotion capabilities
title_full Tumour cell-derived exosomes endow mesenchymal stromal cells with tumour-promotion capabilities
title_fullStr Tumour cell-derived exosomes endow mesenchymal stromal cells with tumour-promotion capabilities
title_full_unstemmed Tumour cell-derived exosomes endow mesenchymal stromal cells with tumour-promotion capabilities
title_short Tumour cell-derived exosomes endow mesenchymal stromal cells with tumour-promotion capabilities
title_sort tumour cell-derived exosomes endow mesenchymal stromal cells with tumour-promotion capabilities
topic Short Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5116561/
https://www.ncbi.nlm.nih.gov/pubmed/27132512
http://dx.doi.org/10.1038/onc.2016.131
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