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

被引：170

作者：

Dong, Liyang ^{[1
]}

Pu, Yanan ^{[1
]}

Zhang, Lina ^{[1
]}

Qi, Qianqian ^{[1
]}

Xu, Lei ^{[1
]}

Li, Wei ^{[1
]}

Wei, Chuan ^{[1
]}

Wang, Xiaofan ^{[1
]}

Zhou, Sha ^{[1
]}

Zhu, Jifeng ^{[1
]}

Wang, Xuefeng ^{[2
]}

Liu, Feng ^{[1
]}

Chen, Xiaojun ^{[1
]}

Su, Chuan ^{[1
]}

机构：

[1] Nanjing Med Univ, Jiangsu Key Lab Pathogen Biol, State Key Lab Reprod Med, Dept Pathogen Biol & Immunol, Nanjing 211166, Jiangsu, Peoples R China

[2] Jiangsu Univ, Affiliated Hosp, Cent Lab, Zhenjiang 212002, Jiangsu, Peoples R China

来源：

CELL DEATH & DISEASE | 2018年 / 9卷

基金：

中国国家自然科学基金;

关键词：

STROMAL CELLS; CANCER-CELLS; TUMOR-GROWTH; INDUCED APOPTOSIS; DOWN-REGULATION; PROLIFERATION; EXPRESSION; TARGETS; NSCLC; MICROVESICLES;

D O I：

10.1038/s41419-018-0323-5

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

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.

引用

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