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Integrin α6-containing extracellular vesicles promote lymphatic remodelling for pre-metastatic niche formation in lymph nodes via interplay with CD151

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资源类型：
WOS体系：
Pubmed体系：

收录情况： ◇ SCIE

作者：
Lin Yan[1,2] * ; Zheng Hanhao[1,2] * ; Jia Linpei[3] * ; Luo Yuming[4] * ; Zhang Dingwen[4] ; An Mingjie[1,2] ; Pang Mingrui[1,2] ; Diao Xiayao[5] ; Li Wenjie[1,2] ; Chen Jiancheng[1,2] ; Li Yuanlong[1,2] ; Liu Daiyin[1,2] ; Liu Zhicong[1,2] ; Huang Jian[1,2] ; Lin Tianxin[1,2,6,*1] ; Chen Changhao[1,2,*1] ;
机构： [1]Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P. R. China. [2]Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, State Key Laboratory of Oncology in South China, Guangzhou, Guangdong, P. R. China. [3]Department of Nephrology, Xuanwu Hospital, Capital Medical University, Beijing, P. R. China. [4]Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, P. R. China. [5]Department of Thoracic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. [6]Department of Urology, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong, P. R. China.
出处：
DOI： 10.1002/jev2.12518

关键词： bladder cancer extracellular vesicles ITGA6 lymphatic metastasis pre-metastatic niche

摘要：
Heterogeneous extracellular vesicles (EVs) from various types of tumours are acknowledged for inducing the formation of pre-metastatic "niches" in draining lymph nodes (LNs) to promote lymphatic metastasis. In order to identify the specific subpopulations of EVs involved, we performed high-resolution proteomic analysis combined with nanoflow cytometry of bladder cancer (BCa) tissue-derived EVs to identify a novel subset of tumour-derived EVs that contain integrin α6 (ITGA6+EVs) and revealed the positive correlation of ITGA6+EVs with the formation of pre-metastatic niche in draining LNs and lymphatic metastasis in multicentre clinical analysis of 820-case BCa patients. BCa-derived ITGA6+EVs induced E-selectin (SELE)-marked lymphatic remodelling pre-metastatic niche and promoted metastasis in draining LNs through delivering cargo circRNA-LIPAR to lymphatic endothelial cells in vivo and in vitro. Mechanistically, LIPAR linked ITGA6 to the switch II domain of RAB5A and sustained RAB5A GTP-bound activated state, thus maintaining the production of ITGA6+EVs loaded with LIPAR through endosomal trafficking. ITGA6+EVs targeted lymphatic vessels through ITGA6-CD151 interplay and released LIPAR to induce SELE overexpression-marked lymphatic remodelling pre-metastatic niche. Importantly, we constructed engineered-ITGA6 EVs to inhibit lymphatic pre-metastatic niche, which suppressed lymphatic metastasis and prolonged survival in preclinical models. Collectively, our study uncovers the mechanism of BCa-derived ITGA6+EVs mediating pre-metastatic niche and provides an engineered-EV-based strategy against BCa lymphatic metastasis.© 2024 The Author(s). Journal of Extracellular Vesicles published by Wiley Periodicals LLC on behalf of International Society for Extracellular Vesicles.

基金：
the National Key Research and Development Program of China, Grant/Award Number: 2022YFA1305500; the National Natural Science Foundation of China, Grant/Award Numbers: 32322023, 82173272, 81825016, 82173230, 82341018, 82203662, 82173271, 82103416, 82103536, 82173266, 82202276, 81972385; the Key Areas Research and Development Program of Guangdong, Grant/Award Numbers: 2022B1515120086, 2021B1515020091, 2022A1515140175, 2021A1515010215, 2023A1515011648, 2022A1515012288, 2021A1515010355; the Science and Technology Program of Guangzhou, China, Grant/Award Numbers: 2023A04J2206, 2023QNYXZD003, 2024A04J6560; Medical Scientific Research Foundation of Guangdong Province, China, Grant/Award Number: A2022117
语种：
外文
被引次数：
WOS：
PubmedID：
中科院(CAS)分区：
出版当年[2023]版：
大类 | 1 区 医学
小类 | 2 区 细胞生物学
最新[2023]版：
大类 | 1 区 医学
小类 | 2 区 细胞生物学
JCR分区：
出版当年[2022]版：
Q1 CELL BIOLOGY
最新[2023]版：
Q1 CELL BIOLOGY

影响因子： 最新[2023版] 最新五年平均 出版当年[2022版] 出版当年五年平均 出版前一年[2021版] 出版后一年[2023版]

第一作者：
第一作者机构： [1]Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P. R. China. [2]Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, State Key Laboratory of Oncology in South China, Guangzhou, Guangdong, P. R. China.
共同第一作者：
通讯作者：
通讯机构： [1]Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P. R. China. [2]Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, State Key Laboratory of Oncology in South China, Guangzhou, Guangdong, P. R. China. [6]Department of Urology, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong, P. R. China. [*1]Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yanjiangxi Road, Yuexiu District, Guangzhou 510120, Guangdong, P. R. China
推荐引用方式(GB/T 7714)：
Lin Yan,Zheng Hanhao,Jia Linpei,et al.Integrin α6-containing extracellular vesicles promote lymphatic remodelling for pre-metastatic niche formation in lymph nodes via interplay with CD151[J].Journal Of Extracellular Vesicles.2024,13(10):e12518.doi:10.1002/jev2.12518.
APA：
Lin Yan,Zheng Hanhao,Jia Linpei,Luo Yuming,Zhang Dingwen...&Chen Changhao.(2024).Integrin α6-containing extracellular vesicles promote lymphatic remodelling for pre-metastatic niche formation in lymph nodes via interplay with CD151.Journal Of Extracellular Vesicles,13,(10)
MLA：
Lin Yan,et al."Integrin α6-containing extracellular vesicles promote lymphatic remodelling for pre-metastatic niche formation in lymph nodes via interplay with CD151".Journal Of Extracellular Vesicles 13..10(2024):e12518

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