{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T01:11:32Z","timestamp":1792026692550,"version":"4.4.0"},"reference-count":82,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2025,1,30]],"date-time":"2025-01-30T00:00:00Z","timestamp":1738195200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"AIRC per la Ricerca sul Cancro","award":["IG 18851"],"award-info":[{"award-number":["IG 18851"]}]},{"name":"AIRC per la Ricerca sul Cancro","award":["IG 24905"],"award-info":[{"award-number":["IG 24905"]}]},{"name":"FRRB grant NEVERMIND","award":["CP2_16\/2018"],"award-info":[{"award-number":["CP2_16\/2018"]}]},{"DOI":"10.13039\/501100004710","name":"Fondazione Umberto Veronesi","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004710","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Plan for Complementary Investments","award":["CUP B53C22006100001"],"award-info":[{"award-number":["CUP B53C22006100001"]}]},{"DOI":"10.13039\/501100021856","name":"Ministero dell\u2019Universit\u00e0 e della Ricerca","doi-asserted-by":"crossref","award":["PRIN2020PBS5MJ"],"award-info":[{"award-number":["PRIN2020PBS5MJ"]}],"id":[{"id":"10.13039\/501100021856","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000928","name":"Welch Foundation","doi-asserted-by":"publisher","award":["AQ-1507"],"award-info":[{"award-number":["AQ-1507"]}],"id":[{"id":"10.13039\/100000928","id-type":"DOI","asserted-by":"publisher"}]},{"name":"AIRC fellowship for Italy","award":["22546"],"award-info":[{"award-number":["22546"]}]},{"DOI":"10.13039\/501100004710","name":"Fondazione Umberto Veronesi","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004710","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Although invasiveness is one of the major determinants of the poor glioblastoma (GBM) outcome, the mechanisms of GBM invasion are only partially understood. Among the intrinsic and environmental processes promoting cell-to-cell interaction processes, eventually driving GBM invasion, we focused on the pro-invasive role played by extracellular vesicles (EVs), a heterogeneous group of cell-released membranous structures containing various bioactive cargoes, which can be transferred from donor to recipient cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Extracellular vesicles isolated from patient-derived GBM cell lines and surgical aspirates were assessed for their pro-migratory competence by spheroid migration assays, calcium imaging, and PYK2\/FAK phosphorylation. Brain invasiveness was investigated in human cortical organoids-based assembloids and in vivo orthotopic xenografts. Extracellular vesicles\u2019 molecular features were specified by multiplex bead-based flow cytometry.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Results unveil a self-sustaining mechanism triggering migration through autocrine release and engagement of a specific population of EVs of large size (L-EVs), isolated from either patient-derived cell lines or surgical aspirates. Large size-EVs act through modulation of calcium transients via Connexin 43-Gap Junctions (Cx43-GJ) and phospho-activation of PYK2. Preincubation with blocking antibodies targeting Cx43 hemichannels demonstrated a dose-dependent inhibition of the L-EV-mediated GBM migration. By exploiting patients\u2019 surgical aspirates, we show that only L-EVs deriving from tumoral cells, and not those with immune origin, promote tumor migration, impacting more prominently the tumoral cells with mesenchymal subtype.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We demonstrate that L-EVs released by GBM cells, but not by the immune cells of the tumor microenvironment, represent a relevant and unique autocrine pro-migratory input for the tumor.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/neuonc\/noaf013","type":"journal-article","created":{"date-parts":[[2025,1,20]],"date-time":"2025-01-20T07:15:54Z","timestamp":1737357354000},"page":"2843-2860","source":"Crossref","is-referenced-by-count":15,"title":["Extracellular vesicles released by glioblastoma cancer cells drive tumor invasiveness via Connexin-43 gap 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Milano, 20089 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Saulle","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Humanitas University , Pieve Emanuele, Milano, 20072 ,","place":["Italy"]},{"name":"IRCCS Humanitas Research Hospital , Rozzano, Milano, 20089 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria C","family":"Gagliani","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Structural Biology, University of Texas Health Science Center at San Antonio , San Antonio, Texas 78229 ,","place":["USA"]},{"name":"Department of Experimental Medicine (DIMES), Cellular Electron Microscopy Laboratory, Universit\u00e0 di Genova , Genova, 16132 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Pizzocri","sequence":"additional","affiliation":[{"name":"IRCCS Humanitas Research Hospital , 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