Cancer-derived exosomal miR-25-3p promotes pre-metastatic niche formation by inducing vascular permeability and angiogenesis

被引：783

作者：

Zeng, Zhicheng ^{[1
,2
,3
]}

Li, Yuling ^{[2
,4
]}

Pan, Yangjian ^{[5
]}

Lan, Xiaoliang ^{[6
]}

Song, Fuyao ^{[1
,2
,3
]}

Sun, Jingbo ^{[5
]}

Zhou, Kun ^{[5
]}

Liu, Xiaolong ^{[5
]}

Ren, Xiaoli ^{[1
,2
,3
]}

Wang, Feifei ^{[1
,2
,3
]}

Hu, Jinlong ^{[1
,2
,3
]}

Zhu, Xiaohui ^{[1
,2
,3
]}

Yang, Wei ^{[1
,2
,3
]}

Liao, Wenting ^{[1
,2
,3
]}

Li, Guoxin ^{[6
]}

Ding, Yanqing ^{[1
,2
,3
]}

Liang, Li ^{[1
,2
,3
]}

机构：

[1] Southern Med Univ, Nanfang Hosp, Dept Pathol, Guangzhou 510515, Guangdong, Peoples R China

[2] Southern Med Univ, Dept Pathol, Guangzhou 510515, Guangdong, Peoples R China

[3] Guangdong Prov Key Lab Mol Tumor Pathol, Guangzhou 510515, Guangdong, Peoples R China

[4] Dongguan Peoples Hosp, Dept Pathol, Dongguan, Guangdong, Peoples R China

[5] Southern Med Univ, Affiliated Hosp 3, Dept Gen Surg, Guangzhou, Guangdong, Peoples R China

[6] Southern Med Univ, Nanfang Hosp, Dept Gen Surg, Guangzhou 510515, Guangdong, Peoples R China

来源：

NATURE COMMUNICATIONS | 2018年 / 9卷

基金：

中国博士后科学基金; 国家重点研发计划; 中国国家自然科学基金;

关键词：

CELL LUNG-CANCER; EXTRACELLULAR VESICLES; MOTILITY; GROWTH; PROLIFERATION; APOPTOSIS; INITIATE;

D O I：

10.1038/s41467-018-07810-w

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Cancer-derived exosomes are considered a major driver of cancer-induced pre-metastatic niche formation at foreign sites, but the mechanisms remain unclear. Here, we show that miR-25-3p, a metastasis-promoting miRNA of colorectal cancer (CRC), can be transferred from CRC cells to endothelial cells via exosomes. Exosomal miR-25-3p regulates the expression of VEGFR2, ZO-1, occludin and Claudin5 in endothelial cells by targeting KLF2 and KLF4, consequently promotes vascular permeability and angiogenesis. In addition, exosomal miR-25-3p from CRC cells dramatically induces vascular leakiness and enhances CRC metastasis in liver and lung of mice. Moreover, the expression level of miR-25-3p from circulating exosomes is significantly higher in CRC patients with metastasis than those without metastasis. Our work suggests that exosomal miR-25-3p is involved in pre-metastatic niche formation and may be used as a blood-based biomarker for CRC metastasis.

引用

页数：14

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