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.研究所北京市神经外科研究所首都医科大学附属天坛医院[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.
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.
基金:
CAMS Innovation Fund for Medical Sciences [2017-I2M-3-007]; National Key Research and Development Program of China [2016YFA0101000, 2016YFA0101003]; Beijing Key Laboratory of New Drug Development and Clinical Trial of Stem Cell Therapy [BZ0381]
语种:
外文
被引次数:
WOS:
PubmedID:
中科院(CAS)分区:
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
JCR分区:
出版当年[2017]版:
Q1MEDICINE, RESEARCH & EXPERIMENTALQ2CELL BIOLOGY
最新[2023]版:
Q1CELL & TISSUE ENGINEERINGQ1CELL BIOLOGYQ1MEDICINE, RESEARCH & EXPERIMENTAL
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.
共同第一作者:
通讯作者:
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.
推荐引用方式(GB/T 7714):
Shihua Wang,Xiaodong Su,Meiqian Xu,et al.Exosomes secreted by mesenchymal stromal/stem cell-derived adipocytes promote breast cancer cell growth via activation of Hippo signaling pathway[J].STEM CELL RESEARCH & THERAPY.2019,10(1):-.doi:10.1186/s13287-019-1220-2.
APA:
Shihua Wang,Xiaodong Su,Meiqian Xu,Xian Xiao,Xiaoxia Li...&Robert Chunhua Zhao.(2019).Exosomes secreted by mesenchymal stromal/stem cell-derived adipocytes promote breast cancer cell growth via activation of Hippo signaling pathway.STEM CELL RESEARCH & THERAPY,10,(1)
MLA:
Shihua Wang,et al."Exosomes secreted by mesenchymal stromal/stem cell-derived adipocytes promote breast cancer cell growth via activation of Hippo signaling pathway".STEM CELL RESEARCH & THERAPY 10..1(2019):-