Human umbilical cord mesenchymal stem cell-derived extracellular vesicles promote lung adenocarcinoma growth by transferring miR-410

Although accumulating evidence has linked mesenchymal stem cells (MSCs) with tumor growth, the underlying mechanisms are poorly understood. Here, we demonstrated for the first time that human umbilical cord MSCs (hUCMSCs) dramatically increased the growth of lung adenocarcinoma (LUAD) cancer cells i...

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Bibliographic Details
Published in:Cell death & disease 2018-02, Vol.9 (2), p.218-13, Article 218
Main Authors: Dong, Liyang, Pu, Yanan, Zhang, Lina, Qi, Qianqian, Xu, Lei, Li, Wei, Wei, Chuan, Wang, Xiaofan, Zhou, Sha, Zhu, Jifeng, Wang, Xuefeng, Liu, Feng, Chen, Xiaojun, Su, Chuan
Format: Article
Language:English
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Adenocarcinoma
Adenocarcinoma of Lung - genetics
Adenocarcinoma of Lung - metabolism
Adenocarcinoma of Lung - pathology
Animals
Antibodies
Apoptosis
Biochemistry
Biomedical and Life Sciences
Cell Biology
Cell Culture
Cell Differentiation - physiology
Cell proliferation
Extracellular vesicles
Extracellular Vesicles - genetics
Extracellular Vesicles - metabolism
Female
Heterografts
Humans
Immunology
Life Sciences
Lung cancer
Male
Mesenchymal Stem Cells - metabolism
Mesenchymal Stem Cells - pathology
Mesenchyme
Mice
MicroRNAs - genetics
MicroRNAs - metabolism
miRNA
PTEN protein
Stem cells
Umbilical cord
Umbilical Cord - metabolism
Umbilical Cord - pathology
Xenografts
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Summary:Although accumulating evidence has linked mesenchymal stem cells (MSCs) with tumor growth, the underlying mechanisms are poorly understood. Here, we demonstrated for the first time that human umbilical cord MSCs (hUCMSCs) dramatically increased the growth of lung adenocarcinoma (LUAD) cancer cells in a xenograft tumor model. Then, we observed that hUCMSC-derived extracellular vesicles (hUCMSC-EVs) contribute to the hUCMSC-promoted LUAD cell growth through a direct effect on LUAD cells. Furthermore, we showed that hUCMSC-EV-mediated LUAD growth is associated with increased proliferation and decreased apoptosis in LUAD cells, concomitant with reduced PTEN expression mediated by the hUCMSC-EV-transmitted miR-410. Our findings provide novel insights into the intercellular communications between cancer cells and MSCs through MSC-EV-miRNA and suggest that modification of hUCMSC-EVs might be an attractive therapeutic option for the clinical application of hUCMSC-EVs that would reduce unwanted side effects.
ISSN:2041-4889
2041-4889
DOI:10.1038/s41419-018-0323-5