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These miRNAs are released into the bloodstream, presumed within extracellular\u2010vesicles (EVs) and represent promising biomarkers. Here, we comprehensively examined the role of EVs, and their miRNA cargo, on (fibroblast\/endothelial\/macrophage) cells representative of the testicular GCT (TGCT) tumour microenvironment (TME). Small RNA next\u2010generation\u2010sequencing was performed on 34 samples, comprising representative malignant GCT cell lines\/EVs and controls (testis fibroblast [Hs1.Tes] cell\u2010line\/EVs and testis\/ovary samples). TME cells received TGCT co\u2010culture, TGCT\u2010derived EVs, and a miRNA overexpression system (miR\u2010371a\u2010OE) to assess functional relevance. TGCT cells secreted EVs into culture media. MiR\u2010371~373 and miR\u2010302\/367 cluster miRNAs were overexpressed in all TGCT cells\/subtypes compared with control cells and were highly abundant in TGCT\u2010derived EVs, with miR\u2010371a\u20103p\/miR\u2010371a\u20105p the most abundant. TGCT co\u2010culture resulted in increased levels of miRNAs from the miR\u2010371~373 and miR\u2010302\/367 clusters in TME (fibroblast) cells. Next, fluorescent labelling demonstrated TGCT\u2010derived EVs were internalised by all TME (fibroblast\/endothelial\/macrophage) cells. TME (fibroblast\/endothelial) cell treatment with EVs derived from different TGCT subtypes resulted in increased miR\u2010371~373 and miR\u2010302\/367 miRNA levels, and other generic (eg, miR\u2010205\u20105p\/miR\u2010148\u20103p) and subtype\u2010specific (seminoma, eg, miR\u2010203a\u20103p; yolk\u2010sac\u2010tumour, eg, miR\u2010375\u20103p) miRNAs. MiR\u2010371a\u2010OE in TME cells resulted in increased collagen contraction (fibroblasts) and angiogenesis (endothelial cells), via direct mRNA downregulation and alteration of relevant pathways. TGCT cells communicate with nontumour stromal TME cells through release of EVs enriched in oncogenic miRNAs, potentially contributing to tumour progression.<\/jats:p>","DOI":"10.1002\/ijc.34697","type":"journal-article","created":{"date-parts":[[2023,8,26]],"date-time":"2023-08-26T07:10:28Z","timestamp":1693033828000},"page":"372-388","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Testicular germ cell tumour cells release <scp>microRNA<\/scp>\u2010containing extracellular vesicles that induce phenotypic and genotypic changes in cells of the tumour microenvironment"],"prefix":"10.1002","volume":"154","author":[{"given":"Luz","family":"Alonso\u2010Crisostomo","sequence":"first","affiliation":[{"name":"Department of Pathology University of Cambridge  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Trendell","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Cambridge  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Ferraresso","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Cambridge  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shivani","family":"Bailey","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Cambridge  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dawn","family":"Ward","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Cambridge  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zachary G. L.","family":"Scurlock","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Cambridge  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie C.","family":"Wenlock","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Cambridge  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos A. P.","family":"Bastos","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine University of Cambridge  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravin","family":"Jugdaohsingh","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine University of Cambridge  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nuno J.","family":"Faria","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine University of Cambridge  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anton J.","family":"Enright","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Cambridge  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cinzia G.","family":"Scarpini","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Cambridge  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Coleman","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Cambridge  Cambridge UK"},{"name":"Department of Histopathology Cambridge University Hospitals NHS Foundation Trust  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4480-1147","authenticated-orcid":false,"given":"Matthew J.","family":"Murray","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Cambridge  Cambridge UK"},{"name":"Department of Paediatric Haematology and Oncology Cambridge University Hospitals NHS Foundation Trust  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,8,26]]},"reference":[{"key":"e_1_2_11_2_1","unstructured":"Cancer Statistics Review 1975\u20102017 \u2013 SEER Statistics [Internet].https:\/\/seer.cancer.gov\/archive\/csr\/1975_2017\/. 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