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Intercellular communication between cancer and stromal cells via extracellular vesicles (EVs) is crucial for the premetastatic microenvironment preparation leading to tumour metastasis. This study shows that under the influence of bioactive peptides derived from the extracellular matrix microenvironment, illustrated here by the AG\u20109 elastin\u2010derived peptide (EDP), PDAC cells secrete more tumour\u2010derived EVs. Compared to PDAC\u2010derived EVs, tumour\u2010derived EVs resulting from AG\u20109 treatment (PDAC AG\u20109\u2010derived EVs) significantly stimulated cell proliferation. At constant amount, tumour\u2010derived EVs were similarly taken up by PDAC and HMEC\u20101 cells. Tumour\u2010derived EVs stimulated cell proliferation, migration, proteinase secretion, and angiogenesis. Bioluminescence imaging allowed tumour\u2010derived EV\/FLuc+ tracking in vivo in a PDAC mouse model. The biodistribution of PDAC AG\u20109\u2010derived EVs was different to PDAC\u2010derived EVs. Our results demonstrate that the microenvironment, through EDP release, may not only influence the genesis of EVs but may also affect tumour progression (tumour growth and angiogenesis), and metastatic homing by modifying the in vivo biodistribution of tumour\u2010derived EVs. They are potential candidates for targeted drug delivery and modulation of tumour progression, and they constitute a new generation of therapeutic tools, merging oncology and genic therapy.<\/jats:p>","DOI":"10.1002\/jex2.145","type":"journal-article","created":{"date-parts":[[2024,3,7]],"date-time":"2024-03-07T06:08:49Z","timestamp":1709791729000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Dysregulation of intercellular communication in vitro and in vivo via extracellular vesicles secreted by pancreatic duct adenocarcinoma cells and generated under the influence of the AG9 elastin peptide\u2010conditioned microenvironment"],"prefix":"10.1002","volume":"3","author":[{"given":"Lise","family":"Nannan","sequence":"first","affiliation":[{"name":"Universit\u00e9 de Reims Champagne\u2010Ardenne Laboratoire de Biochimie M\u00e9dicale et Biologie Mol\u00e9culaire, UFR M\u00e9decine  Reims France"},{"name":"CNRS UMR 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