微泡
转移
癌症研究
肿瘤微环境
外体
封堵器
血管通透性
结直肠癌
癌细胞
上皮-间质转换
医学
小RNA
癌症
生物
免疫学
病理
细胞生物学
内科学
紧密连接
肿瘤细胞
生物化学
基因
作者
Keshu Liu,Rongzhang Dou,Chaogang Yang,Ziyang Di,Dongdong Shi,Chunxiao Zhang,Jialin Song,Yan Fang,Sihao Huang,Zhenxian Xiang,Weisong Zhang,Shuyi Wang,Bin Xiong
出处
期刊:Carcinogenesis
[Oxford University Press]
日期:2023-03-20
卷期号:44 (4): 356-367
被引量:9
标识
DOI:10.1093/carcin/bgad013
摘要
Metastasis is the leading cause of colorectal cancer treatment failure and mortality. Communication between endothelium and tumor cells in the tumor microenvironment is required for cancer metastasis. Tumor-derived exosomes have been shown to increase vascular permeability by delivering microRNA (miRNA) to vascular endothelial cells, facilitating cancer metastasis. The mechanism by which Epithelial-mesenchymal transition (EMT) tumor cell-derived exosomes influence vascular permeability remains unknown. MicroRNA-29a (miR-29a) expression is up-regulated in colorectal cancer (CRC) tissues, which is clinically significant in metastasis. Exosomal miR-29a secreted by EMT-CRC cells has been found to decrease the expression of Zonula occlusion 1 (ZO-1), Claudin-5, and Occludin via targeting Kruppel-like factor 4 (KLF4). In vitro co-culture investigations further revealed that EMT-cancer cells release exosomal miR-29a, which alters vascular endothelial permeability. Furthermore, exosomal miR-29a promoted liver metastases in CRC mice. Our findings demonstrate that EMT-CRC cells may transport exosomal miR-29a to endothelial cells in the tumor microenvironment (TME). As a result, increased vascular permeability promotes the development and metastasis of CRC. Exosomal miR-29a has the potential to be a predictive marker for tumor metastasis as well as a viable therapeutic target for CRC.
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