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While the value of 3D conditions to study tumor cells is well established, the impact of cellular architecture on EV content and function is not investigated yet. Here, a recently developed 3D cell culture microwell array is adapted for EV production and a comprehensive comparative analysis of biochemical features, RNA and proteomic profiles of EVs secreted by 2D vs 3D cultures of gastric cancer cells, is performed. 3D cultures are significantly more efficient in producing EVs than 2D cultures. Global upregulation of microRNAs and downregulation of proteins in 3D are observed, indicating their dynamic coregulation in response to cellular architecture, with the ADP\u2010ribosylation factor 6 signaling pathway significantly downregulated in 3D EVs. The data strengthen the biological relevance of cellular architecture for production and cargo of EVs.<\/jats:p>","DOI":"10.1002\/advs.201800948","type":"journal-article","created":{"date-parts":[[2018,12,20]],"date-time":"2018-12-20T05:45:44Z","timestamp":1545284744000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":124,"title":["3D Cellular Architecture Affects MicroRNA and Protein Cargo of Extracellular Vesicles"],"prefix":"10.1002","volume":"6","author":[{"given":"Sara","family":"Rocha","sequence":"first","affiliation":[{"name":"i3S\u2014Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade Universidade do Porto  Rua Alfredo Allen 208 4200\u2010135 Porto Portugal"},{"name":"Ipatimup\u2014Institute of Molecular Pathology and Immunology University of Porto  Rua J\u00falio Amaral de Carvalho 45 4200\u2010135 Porto Portugal"},{"name":"ICBAS\u2014Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar Universidade do Porto  R. 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