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

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机构: [1]Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Center of Excellence in Tissue Engineering Chinese Academy of Medical Sciences, Beijing 100005, China. [2]Brain Tumor Research Center, Beijing Neurosurgical Institute, Beijing Tiantan Hospital affiliated to Capital Medical University, Tiantan Xili 6, Dongcheng District, Beijing 100050, China. [3]Department of Genetics and Cell Biology, Basic Medical College, Qingdao University, 308 Ningxia Road, Qingdao 266071, China. [4]Cell Therapy Program, Princess Margaret Hospital, Toronto, Ontario M5G 2M9, Canada. [5]Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario M5G 2M9, Canada. [6]Institute of Medical Science, University of Toronto, Toronto, Ontario M5G 2M9, Canada.
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关键词: Exosomes Adipocyte Mesenchymal stromal/stem cell Breast cancer Hippo signaling pathway

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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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出版当年[2018]版:
大类 | 2 区 医学
小类 | 2 区 医学:研究与实验 3 区 细胞生物学
最新[2023]版:
大类 | 2 区 医学
小类 | 2 区 细胞与组织工程 2 区 细胞生物学 2 区 医学:研究与实验
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出版当年[2017]版:
Q1 MEDICINE, RESEARCH & EXPERIMENTAL Q2 CELL BIOLOGY
最新[2023]版:
Q1 CELL & TISSUE ENGINEERING Q1 CELL BIOLOGY Q1 MEDICINE, RESEARCH & EXPERIMENTAL

影响因子: 最新[2023版] 最新五年平均 出版当年[2017版] 出版当年五年平均 出版前一年[2016版] 出版后一年[2018版]

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第一作者机构: [1]Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Center of Excellence in Tissue Engineering Chinese Academy of Medical Sciences, Beijing 100005, China.
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通讯机构: [1]Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Center of Excellence in Tissue Engineering Chinese Academy of Medical Sciences, Beijing 100005, China. [4]Cell Therapy Program, Princess Margaret Hospital, Toronto, Ontario M5G 2M9, Canada. [5]Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario M5G 2M9, Canada. [6]Institute of Medical Science, University of Toronto, Toronto, Ontario M5G 2M9, Canada.
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