{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T03:04:39Z","timestamp":1791255879879,"version":"4.1.0"},"reference-count":41,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2014,2,6]],"date-time":"2014-02-06T00:00:00Z","timestamp":1391644800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Oncology"],"published-print":{"date-parts":[[2014,5]]},"abstract":"<jats:p>Bone metastasis represents one of the most deleterious clinical consequences arising in the context of many solid tumors. Severe osteolysis results from tumor cell colonization of the bone compartment, a process which entails reciprocal exchange of soluble signals between tumor cells and their osseous microenvironment. Recent evidence indicates that tumor\u2010intrinsic miRNAs are pleiotropic regulators of gene expression. But they are also frequently released in exosome\u2010like vesicles (ELV). Yet the functional relevance of the transference of tumor\u2010derived ELV and their miRNA cargo to the extracellular milieu during osseous colonization is unknown.<\/jats:p><jats:p>Comparative transcriptomic profiling using an <jats:italic>in\u00a0vivo<\/jats:italic> murine model of bone metastasis identified a repressed miRNA signature associated with high prometastatic activity. Forced expression of single miRNAs identified miR\u2010192 that markedly appeased osseous metastasis <jats:italic>in\u00a0vivo<\/jats:italic>, as shown by X\u2010ray, bioluminescence imaging and microCT scans. Histological examination of metastatic lesions revealed impaired tumor\u2010induced angiogenesis <jats:italic>in\u00a0vivo<\/jats:italic>, an effect that was associated <jats:italic>in\u00a0vitro<\/jats:italic> with decreased hallmarks of angiogenesis. Isolation and characterization of ELV by flow cytometry, Western blot analysis, transmission electron microscopy and nanoparticle tracking analysis revealed the ELV cargo enrichment in miR\u2010192. Consistent with these findings, fluorescent labeled miR\u2010192\u2010enriched\u2010ELV showed the <jats:italic>in\u00a0vitro<\/jats:italic> transfer and release of miR\u2010192 in target endothelial cells and abrogation of the angiogenic program by repression of proangiogenic IL\u20108, ICAM and CXCL1. Moreover, <jats:italic>in\u00a0vivo<\/jats:italic> infusion of fluorescent labeled ELV efficiently targeted cells of the osseous compartment. Furthermore, treatment with miR\u2010192 enriched ELV in a model of <jats:italic>in\u00a0vivo<\/jats:italic> bone metastasis pre\u2010conditioned osseous milieu and impaired tumor\u2010induced angiogenesis, thereby reducing the metastatic burden and tumor colonization.<\/jats:p><jats:p>Changes in the miRNA\u2010cargo content within ELV represent a novel mechanism heavily influencing bone metastatic colonization, which is most likely relevant in other target organs. Mechanistic mimicry of this phenomenon by synthetic nanoparticles could eventually emerge as a novel therapeutic approach.<\/jats:p>","DOI":"10.1016\/j.molonc.2014.01.012","type":"journal-article","created":{"date-parts":[[2014,2,6]],"date-time":"2014-02-06T14:45:45Z","timestamp":1391697945000},"page":"689-703","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":157,"title":["miRNA cargo within exosome\u2010like vesicle transfer influences metastatic bone colonization"],"prefix":"10.1002","volume":"8","author":[{"given":"Karmele","family":"Valencia","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego","family":"Luis-Ravelo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Bovy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iker","family":"Ant\u00f3n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susana","family":"Mart\u00ednez-Canarias","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina","family":"Zandueta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Ormaz\u00e1bal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingrid","family":"Struman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e9bastien","family":"Tabruyn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vera","family":"Rebmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"De Las Rivas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabet","family":"Guruceaga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Bandr\u00e9s","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando","family":"Lecanda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,2,6]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1017667108"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-08-1569"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1593\/neo.81282"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-10-1708"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-09-4092"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0142(19971015)80:8 <1588::AID-CNCR9>3.0.CO;2-G"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2005.06.036"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkr232"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1098"},{"key":"e_1_2_9_11_1","first-page":"3433","article-title":"The amount and proteolytic content of vesicles shed by human cancer cell lines correlates with their in\u00a0vitro invasiveness","volume":"18","author":"Ginestra A.","year":"1998","journal-title":"Anticancer Res."},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-11-0241"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118947"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-10-4455"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000259043.42571.68"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature04303"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng2003"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2284"},{"key":"e_1_2_9_19_1","article-title":"A gene signature of bone metastatic colonization sensitizes for tumor-induced osteolysis and predicts survival in lung cancer","author":"Luis-Ravelo D.","year":"2013","journal-title":"Oncogene"},{"key":"e_1_2_9_20_1","article-title":"RHOB influences lung adenocarcinoma metastasis and resistance in a host-sensitive manner","author":"Luis-Ravelo D.","year":"2013","journal-title":"Mol. 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