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Here, we demonstrated that EVs from highly metastatic osteosarcoma cell lines preferentially localized to lung fibroblasts and induce inflammatory PMN formation. High\u2010throughput profiling of EVs\u2010derived long noncoding RNAs (lncRNAs) identified lncOSLMT as a candidate enriched in EVs and markedly upregulated in patient tumors and serum, with elevated levels correlating with poor prognosis. Mechanistically, in EVs, lncOSLMT directly bound the RNA\u2010binding protein hnRNPA2B1. Following internalization by recipient lung fibroblasts, hnRNPA2B1 bound to N\n                    <jats:sup>6<\/jats:sup>\n                    \u2010methyladenosine (m\n                    <jats:sup>6<\/jats:sup>\n                    A) \u2010modified sites in the 3\u2019UTR of\n                    <jats:italic>PTGS2<\/jats:italic>\n                    mRNA, leading to transcript stabilization and increased COX\u20102 expression. For therapeutic intervention, we developed lactoferrin\u2010resveratrol (LF\u2010RES) nanoparticles, which loaded siRNA against lncOSLMT. Intravenous administration of LF\u2010RES\u2010siRNA in mice reduced EVs\u2010induced lung inflammation and suppressed lung metastasis. Combination with EP2\/EP4 antagonists produced enhanced anti\u2010metastatic effects. These findings establish EVs\u2010derived lncOSLMT as a key regulator of inflammatory PMN formation in the lung and highlight the potential of LF\u2010RES\u2010siRNA nanoparticles as a targeted anti\u2010metastatic therapy in osteosarcoma.\n                  <\/jats:p>","DOI":"10.1002\/advs.202519490","type":"journal-article","created":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T04:59:21Z","timestamp":1769057961000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Tumor Extracellular Vesicles lncOSLMT Drives Lung Inflammatory Premetastatic Niche Formation in Osteosarcoma via m\n                    <sup>6<\/sup>\n                    A\u2010Dependent hnRNPA2B1\/COX\u20102 Axis"],"prefix":"10.1002","volume":"13","author":[{"given":"Hongbo","family":"Li","sequence":"first","affiliation":[{"name":"Department of Musculoskeletal Oncology The First Affiliated Hospital of Sun Yat\u2010Sen University  Guangzhou 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