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Exosomes secreted by mesenchymal stromal/stem cell-derived adipocytes promote breast cancer cell growth via activation of Hippo signaling pathway

OBJECTIVE: Although adipocytes are the most abundant stromal cell component in breast cancer tissues, their interaction with breast cancer cells has been less investigated compared to cancer-associated fibroblasts or macrophages. Exosomes are a novel way of cell-cell communication and have been demo...

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Autores principales: Wang, Shihua, Su, Xiaodong, Xu, Meiqian, Xiao, Xian, Li, Xiaoxia, Li, Hongling, Keating, Armand, Zhao, Robert Chunhua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6458638/
https://www.ncbi.nlm.nih.gov/pubmed/30971292
http://dx.doi.org/10.1186/s13287-019-1220-2
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author Wang, Shihua
Su, Xiaodong
Xu, Meiqian
Xiao, Xian
Li, Xiaoxia
Li, Hongling
Keating, Armand
Zhao, Robert Chunhua
author_facet Wang, Shihua
Su, Xiaodong
Xu, Meiqian
Xiao, Xian
Li, Xiaoxia
Li, Hongling
Keating, Armand
Zhao, Robert Chunhua
author_sort Wang, Shihua
collection PubMed
description OBJECTIVE: Although adipocytes are the most abundant stromal cell component in breast cancer tissues, their interaction with breast cancer cells has been less investigated compared to cancer-associated fibroblasts or macrophages. Exosomes are a novel way of cell-cell communication and have been demonstrated to play an important role in various biological processes. However, to our knowledge, only a few studies have reported the effects of adipocyte exosomes on tumor development. Here, utilizing exosomes isolated from in vitro mesenchymal stromal/stem cell (MSC)-differentiated adipocytes, we systematically investigated this issue in a breast cancer model. MATERIAL AND METHODS: Exosomes were isolated from MSC-differentiated adipocytes and added to breast cancer cells MCF7. Cell proliferation was detected by MTS, and migration was analyzed by wound healing and transwell assay. An in vivo mouse xenograft model was used to evaluate MSC-differentiated adipocyte exosomes’ contribution to tumor growth. Signaling pathway activation was evaluated by western blot and immunofluorescence staining. RESULTS: We found MSC-differentiated adipocyte-derived exosomes are actively incorporated by breast cancer cell MCF7 and subsequently promote MCF7 proliferation and migration as well as protect MCF7 from serum derivation or chemotherapeutic drug-induced apoptosis in vitro. In the in vivo mouse xenograft model, depletion of exosomes reduces tumor-promoting effects of adipocytes. Transcriptomic analysis of MSC-differentiated adipocyte exosome-treated MCF7 identified several activated signaling pathways, among which we confirm the Hippo signaling pathway and found a blockade of this pathway leads to a reduced growth-promoting effect of adipocyte exosomes. CONCLUSION: Taken together, our findings provide new insights into the role of adipocyte exosomes in the tumor microenvironment.
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spelling pubmed-64586382019-04-19 Exosomes secreted by mesenchymal stromal/stem cell-derived adipocytes promote breast cancer cell growth via activation of Hippo signaling pathway Wang, Shihua Su, Xiaodong Xu, Meiqian Xiao, Xian Li, Xiaoxia Li, Hongling Keating, Armand Zhao, Robert Chunhua Stem Cell Res Ther Research OBJECTIVE: Although adipocytes are the most abundant stromal cell component in breast cancer tissues, their interaction with breast cancer cells has been less investigated compared to cancer-associated fibroblasts or macrophages. Exosomes are a novel way of cell-cell communication and have been demonstrated to play an important role in various biological processes. However, to our knowledge, only a few studies have reported the effects of adipocyte exosomes on tumor development. Here, utilizing exosomes isolated from in vitro mesenchymal stromal/stem cell (MSC)-differentiated adipocytes, we systematically investigated this issue in a breast cancer model. MATERIAL AND METHODS: Exosomes were isolated from MSC-differentiated adipocytes and added to breast cancer cells MCF7. Cell proliferation was detected by MTS, and migration was analyzed by wound healing and transwell assay. An in vivo mouse xenograft model was used to evaluate MSC-differentiated adipocyte exosomes’ contribution to tumor growth. Signaling pathway activation was evaluated by western blot and immunofluorescence staining. RESULTS: We found MSC-differentiated adipocyte-derived exosomes are actively incorporated by breast cancer cell MCF7 and subsequently promote MCF7 proliferation and migration as well as protect MCF7 from serum derivation or chemotherapeutic drug-induced apoptosis in vitro. In the in vivo mouse xenograft model, depletion of exosomes reduces tumor-promoting effects of adipocytes. Transcriptomic analysis of MSC-differentiated adipocyte exosome-treated MCF7 identified several activated signaling pathways, among which we confirm the Hippo signaling pathway and found a blockade of this pathway leads to a reduced growth-promoting effect of adipocyte exosomes. CONCLUSION: Taken together, our findings provide new insights into the role of adipocyte exosomes in the tumor microenvironment. BioMed Central 2019-04-11 /pmc/articles/PMC6458638/ /pubmed/30971292 http://dx.doi.org/10.1186/s13287-019-1220-2 Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided 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 Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Wang, Shihua
Su, Xiaodong
Xu, Meiqian
Xiao, Xian
Li, Xiaoxia
Li, Hongling
Keating, Armand
Zhao, Robert Chunhua
Exosomes secreted by mesenchymal stromal/stem cell-derived adipocytes promote breast cancer cell growth via activation of Hippo signaling pathway
title Exosomes secreted by mesenchymal stromal/stem cell-derived adipocytes promote breast cancer cell growth via activation of Hippo signaling pathway
title_full Exosomes secreted by mesenchymal stromal/stem cell-derived adipocytes promote breast cancer cell growth via activation of Hippo signaling pathway
title_fullStr Exosomes secreted by mesenchymal stromal/stem cell-derived adipocytes promote breast cancer cell growth via activation of Hippo signaling pathway
title_full_unstemmed Exosomes secreted by mesenchymal stromal/stem cell-derived adipocytes promote breast cancer cell growth via activation of Hippo signaling pathway
title_short Exosomes secreted by mesenchymal stromal/stem cell-derived adipocytes promote breast cancer cell growth via activation of Hippo signaling pathway
title_sort exosomes secreted by mesenchymal stromal/stem cell-derived adipocytes promote breast cancer cell growth via activation of hippo signaling pathway
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6458638/
https://www.ncbi.nlm.nih.gov/pubmed/30971292
http://dx.doi.org/10.1186/s13287-019-1220-2
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