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Tumor\u2010associated macrophages (TAMs), a crucial component of the tumor microenvironment (TME), primarily adopt a metastasis\u2010promoting M2 phenotype. However, the mechanisms underlying the TAM\u2010cancer cell crosstalk and resultant PCa metastasis remain elusive. In this study, primary lesions of metastatic PCa (mPCa) exhibit both greater infiltration of M2 macrophages and a higher proportion of M2 macrophage\u2010derived extracellular vesicles (M2 EVs) compared to those of non\u2010metastatic PCa (nmPCa). Furthermore, M2 EVs can be internalized by PCa cells, promoting a mesenchymal\u2010like state (MLS) in PCa and affecting tumor metastasis. Mechanistically, thioredoxin domain\u2010containing 5 (\n                    <jats:italic>TXNDC5<\/jats:italic>\n                    ) mRNA encapsulated in M2 EVs contributes to MLS of DU145 and PC3 cells, enhancing migration and invasion. Single\u2010vesicle particle analysis confirms that\n                    <jats:italic>TXNDC5<\/jats:italic>\n                    mRNA encapsulated within M2 EVs can be horizontally transferred to target cells, where it is translated to produce functional proteins. In conclusion, our study demonstrates that M2 macrophages can promote MLS and metastasis of PCa through EV\u2010mediated horizontal mRNA transfer. A novel role of EVs in the communication between the TME and tumor cells is discovered, offering new insights into tumor metastasis.\n                  <\/jats:p>","DOI":"10.1002\/advs.202511052","type":"journal-article","created":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T13:19:52Z","timestamp":1770124792000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Intercellular Horizontal Transfer of TXNDC5 mRNA via Extracellular Vesicles Contributes to Tumor\u2010Associated Macrophage\u2010Mediated Prostate Cancer Metastasis"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6503-7750","authenticated-orcid":false,"given":"Cong","family":"Hu","sequence":"first","affiliation":[{"name":"Department of Urology Ren Ji Hospital Shanghai Jiao Tong University School of Medicine  Shanghai 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