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This study aimed to examine the involvement and mechanism of integrin subunit beta 3 (ITGB3) in the process of LUAD bone metastasis. Our findings indicate that ITGB3 facilitates the migration and invasion of LUAD cells in vitro and metastasis to the bone in vivo. Furthermore, ITGB3 stimulates osteoclast production and activation, thereby expediting osteolytic lesion progression. Extracellular vesicles (EVs) isolated from the conditioned medium (CM) of LUAD cells overexpressing ITGB3 determined that ITGB3 facilitates osteoclastogenesis and enhances osteoclast activity by utilizing EVs\u2010mediated transport to RAW264.7 cells. Our in vivo findings demonstrated that ITGB3\u2010EVs augmented the population of osteoclasts, thereby establishing an osteoclastic pre\u2010metastatic niche (PMN) conducive to the colonization and subsequent growth of LUAD cells in the bone. ITGB3 is enriched in serum EVs of patients diagnosed with LUAD bone metastasis, potentially facilitating osteoclast differentiation and activation in vitro. Our research illustrates that ITGB3\u2010EVs derived from LUAD cells facilitate osteoclast differentiation and activation by modulating the phosphorylation level of p38 MAPK. This process ultimately leads to the generation of osteolytic PMN and accelerates the progression of bone metastasis.<\/jats:p>","DOI":"10.1002\/mc.23803","type":"journal-article","created":{"date-parts":[[2024,8,13]],"date-time":"2024-08-13T18:09:04Z","timestamp":1723572544000},"page":"2190-2204","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["ITGB3\u2010enriched extracellular vesicles mediate the formation of osteoclastic pre\u2010metastatic niche to promote lung adenocarcinoma bone metastasis"],"prefix":"10.1002","volume":"63","author":[{"given":"Rong","family":"Qiu","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Deng","sequence":"additional","affiliation":[{"name":"College of Fisheries and 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