{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T12:09:31Z","timestamp":1792238971278,"version":"4.4.0"},"reference-count":54,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2024,9,27]],"date-time":"2024-09-27T00:00:00Z","timestamp":1727395200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Extracellular Vesicle"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Heterogeneous extracellular vesicles (EVs) from various types of tumours are acknowledged for inducing the formation of pre\u2010metastatic \u201cniches\u201d in draining lymph nodes (LNs) to promote lymphatic metastasis. In order to identify the specific subpopulations of EVs involved, we performed high\u2010resolution proteomic analysis combined with nanoflow cytometry of bladder cancer (BCa) tissue\u2010derived EVs to identify a novel subset of tumour\u2010derived EVs that contain integrin \u03b16 (ITGA6\n                    <jats:sup>+<\/jats:sup>\n                    EVs) and revealed the positive correlation of ITGA6\n                    <jats:sup>+<\/jats:sup>\n                    EVs with the formation of pre\u2010metastatic niche in draining LNs and lymphatic metastasis in multicentre clinical analysis of 820\u2010case BCa patients. BCa\u2010derived ITGA6\n                    <jats:sup>+<\/jats:sup>\n                    EVs induced E\u2010selectin (SELE)\u2010marked lymphatic remodelling pre\u2010metastatic niche and promoted metastasis in draining LNs through delivering cargo circRNA\u2010\n                    <jats:italic>LIPAR<\/jats:italic>\n                    to lymphatic endothelial cells in vivo and in vitro. Mechanistically,\n                    <jats:italic>LIPAR<\/jats:italic>\n                    linked ITGA6 to the switch II domain of RAB5A and sustained RAB5A GTP\u2010bound activated state, thus maintaining the production of ITGA6\n                    <jats:sup>+<\/jats:sup>\n                    EVs loaded with\n                    <jats:italic>LIPAR<\/jats:italic>\n                    through endosomal trafficking. ITGA6\n                    <jats:sup>+<\/jats:sup>\n                    EVs targeted lymphatic vessels through ITGA6\u2010CD151 interplay and released\n                    <jats:italic>LIPAR<\/jats:italic>\n                    to induce SELE overexpression\u2010marked lymphatic remodelling pre\u2010metastatic niche. Importantly, we constructed engineered\u2010ITGA6 EVs to inhibit lymphatic pre\u2010metastatic niche, which suppressed lymphatic metastasis and prolonged survival in preclinical models. Collectively, our study uncovers the mechanism of BCa\u2010derived ITGA6\n                    <jats:sup>+<\/jats:sup>\n                    EVs mediating pre\u2010metastatic niche and provides an engineered\u2010EV\u2010based strategy against BCa lymphatic metastasis.\n                  <\/jats:p>","DOI":"10.1002\/jev2.12518","type":"journal-article","created":{"date-parts":[[2024,9,27]],"date-time":"2024-09-27T12:39:54Z","timestamp":1727440794000},"source":"Crossref","is-referenced-by-count":28,"title":["Integrin \u03b16\u2010containing extracellular vesicles promote lymphatic remodelling for pre\u2010metastatic niche formation in lymph nodes via interplay with CD151"],"prefix":"10.1002","volume":"13","author":[{"given":"Yan","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Urology Sun Yat\u2010sen Memorial Hospital, Sun Yat\u2010sen University  Guangzhou Guangdong P. R. 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuming","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of General Surgery Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences  Guangzhou Guangdong P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dingwen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of General Surgery Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences  Guangzhou Guangdong P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingjie","family":"An","sequence":"additional","affiliation":[{"name":"Department of Urology Sun Yat\u2010sen Memorial Hospital, Sun Yat\u2010sen University  Guangzhou Guangdong P. R. 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