{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T19:04:42Z","timestamp":1775156682857,"version":"3.50.1"},"reference-count":44,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2019,5,28]],"date-time":"2019-05-28T00:00:00Z","timestamp":1559001600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"FEDER - Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020 - Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by Portuguese funds through Portuguese Science &amp; Technology Foundation (FCT) \/","award":["POCI-01-0145-FEDER-007274"],"award-info":[{"award-number":["POCI-01-0145-FEDER-007274"]}]},{"name":"Norte Portugal Regional Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF)","award":["NORTE-01-0145-FEDER-000029"],"award-info":[{"award-number":["NORTE-01-0145-FEDER-000029"]}]},{"name":"Portuguese FCT","award":["PTDC\/BBB-ECT\/2518\/2014"],"award-info":[{"award-number":["PTDC\/BBB-ECT\/2518\/2014"]}]},{"name":"FCT PhD Programmes and by Programa Operacional Potencial Humano (POCH)","award":["BiotechHealth Programe (Doctoral Programme on Cellular and Molecular Biotechnology Applied to Health Sciences)"],"award-info":[{"award-number":["BiotechHealth Programe (Doctoral Programme on Cellular and Molecular Biotechnology Applied to Health Sciences)"]}]},{"name":"Ipatimup","award":["\"The role of gastric cancer cell-derived extracellular vesicles\u201d"],"award-info":[{"award-number":["\"The role of gastric cancer cell-derived extracellular vesicles\u201d"]}]},{"name":"FCT fellowships","award":["PD\/BD\/128406\/2017 to SR; SFRH\/BPD\/86543\/2012 to JC; SFRH\/BPD\/89764\/2012 to PO"],"award-info":[{"award-number":["PD\/BD\/128406\/2017 to SR; SFRH\/BPD\/86543\/2012 to JC; SFRH\/BPD\/89764\/2012 to PO"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Extracellular vesicles (EVs) secreted by tumor cells modulate recipient cells\u2019 behavior, but their effects in normal cells from the tumor microenvironment remain poorly known. In this study, we dissected the functional impact of gastric cancer cell-derived EVs (GC-EVs), representative of distinct GC histotypes, on the behavior of normal isogenic epithelial and mesenchymal cells. GC-EVs were isolated by differential centrifugation and characterized by transmission electron microscopy, nanoparticle tracking analysis, and imaging flow-cytometry. Epithelial and mesenchymal cells were challenged with GC-EVs and submitted to proliferation, migration, and invasion assays. Expression of epithelial and mesenchymal markers was followed by immunofluorescence and flow-cytometry. Our results indicated that GC-EVs secreted by diffuse-type cancer cells decrease the migration of recipient cells. This effect was more prominent and persistent for mesenchymal recipient cells, which also increased Fibronectin expression in response to EVs. GC-EVs secreted by cancer cells derived from tumors with an intestinal component increased invasion of recipient epithelial cells, without changes in EMT markers. In summary, this study demonstrated that GC-EVs modulate the migration and invasion of epithelial and mesenchymal cells from the tumor microenvironment, in a histotype-dependent manner, highlighting new features of intestinal and diffuse-type GC cells, which may help explaining differential metastasis patterns and aggressiveness of GC histotypes.<\/jats:p>","DOI":"10.3390\/ijms20112608","type":"journal-article","created":{"date-parts":[[2019,5,28]],"date-time":"2019-05-28T11:18:09Z","timestamp":1559042289000},"page":"2608","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Gastric Cancer Extracellular Vesicles Tune the Migration and Invasion of Epithelial and Mesenchymal Cells in a Histotype-Dependent Manner"],"prefix":"10.3390","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5390-3807","authenticated-orcid":false,"given":"Sara","family":"Rocha","sequence":"first","affiliation":[{"name":"i3S\u2013Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"Ipatimup\u2014Institute of Molecular Pathology and Immunology of University of Porto, 4200-135 Porto, Portugal"},{"name":"ICBAS\u2014Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar, Universidade do Porto, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7409-9651","authenticated-orcid":false,"given":"Sara Pinto","family":"Teles","sequence":"additional","affiliation":[{"name":"i3S\u2013Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"Ipatimup\u2014Institute of Molecular Pathology and Immunology of University of Porto, 4200-135 Porto, Portugal"}]},{"given":"Mafalda","family":"Azevedo","sequence":"additional","affiliation":[{"name":"ICBAS\u2014Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar, Universidade do Porto, 4050-313 Porto, Portugal"},{"name":"Program in Developmental Biology, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA"}]},{"given":"Patr\u00edcia","family":"Oliveira","sequence":"additional","affiliation":[{"name":"i3S\u2013Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"Ipatimup\u2014Institute of Molecular Pathology and Immunology of University of Porto, 4200-135 Porto, Portugal"}]},{"given":"Joana","family":"Carvalho","sequence":"additional","affiliation":[{"name":"i3S\u2013Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"Ipatimup\u2014Institute of Molecular Pathology and Immunology of University of Porto, 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8340-2264","authenticated-orcid":false,"given":"Carla","family":"Oliveira","sequence":"additional","affiliation":[{"name":"i3S\u2013Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"Ipatimup\u2014Institute of Molecular Pathology and Immunology of University of Porto, 4200-135 Porto, Portugal"},{"name":"Department Pathology, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2019,5,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"18","DOI":"10.3389\/fcell.2018.00018","article-title":"Exosome-based cell-cell communication in the tumor microenvironment","volume":"6","author":"Maia","year":"2018","journal-title":"Front. 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