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The activation of cancer-associated fibroblasts (CAFs) is a key element in tumor progression and can be triggered by cancer-derived extracellular vesicles (EVs). Targeting the communication between cancer cells and the surrounding tumor microenvironment (TME) may control cancer progression. Our aim was to investigate the effect of ASA on breast cancer cells, focusing on EV secretion and their effect on the biological properties of CAFs. As a result, ASA was shown to reduce the amount and alter the size distribution of EVs produced by MDA-MB-231 tumor cells. Fibroblasts stimulated with EVs derived from MDA-MB-231 treated with ASA (EV-ASA) showed a lower expression of alpha-smooth muscle actin (\u03b1-SMA), matrix metalloproteinase-2 (MMP2) but not fibroblast activation protein (FAP) in respect to the ones stimulated with EVs from untreated breast cancer cells (EV-CTR). Furthermore, invasion assays using a three-dimensional (3D) fibroblast spheroid model showed reduced MDA-MB-231 invasion towards fibroblast spheroids pretreated with EV-ASA as compared to spheroids prepared with EV-CTR-stimulated fibroblasts. This suggests that ASA partially inhibits the ability of tumor EVs to stimulate CAFs to promote cancer invasion. In conclusion, ASA can interfere with tumor communication by reducing EV secretion by breast tumor cells as well as by interfering with their capacity to stimulate fibroblasts to become CAFs.<\/jats:p>","DOI":"10.3390\/ijms241512020","type":"journal-article","created":{"date-parts":[[2023,7,28]],"date-time":"2023-07-28T01:51:47Z","timestamp":1690509107000},"page":"12020","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Aspirin Affects MDA-MB-231 Vesicle Production and Their Capacity to Induce Fibroblasts towards a Pro-Invasive State"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8366-0343","authenticated-orcid":false,"given":"Rafaela de Assiz","family":"Louback","sequence":"first","affiliation":[{"name":"Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro 21941590, Brazil"},{"name":"Clementino Fraga Filho University Hospiyal, Federal University of Rio de Janeiro, Rio de Janeiro 21941913, Brazil"},{"name":"Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro 21941590, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karina","family":"Martins-Cardoso","sequence":"additional","affiliation":[{"name":"Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro 21941590, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1299-6242","authenticated-orcid":false,"given":"Luzineide W.","family":"Tinoco","sequence":"additional","affiliation":[{"name":"Laboratory for Analysis and Development of Enzyme Inhibitors, Natural Products Research Institute, Federal University of Rio de Janeiro, Rio de Janeiro 21941590, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3619-7701","authenticated-orcid":false,"given":"Federica","family":"Collino","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences and Community Health, University of Milano, 20122 Milan, Italy"},{"name":"Laboratory of Translational Research in Paediatric Nephro-Urology, Fondazione IRCCS Ca\u2019 Granda-Ospedale Maggiore Policlinico, 20122 Milan, Italy"},{"name":"Pediatric Nephrology, Dialysis and Transplant Unit, Fondazione IRCCS Ca\u2019 Granda-Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana Paula D. N.","family":"de Barros","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro 21941590, Brazil"},{"name":"Clementino Fraga Filho University Hospiyal, Federal University of Rio de Janeiro, Rio de Janeiro 21941913, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anneliese","family":"Fortuna-Costa","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro 21941590, Brazil"},{"name":"Clementino Fraga Filho University Hospiyal, Federal University of Rio de Janeiro, Rio de Janeiro 21941913, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5260-2332","authenticated-orcid":false,"given":"Robson Q.","family":"Monteiro","sequence":"additional","affiliation":[{"name":"Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro 21941590, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Isabel Doria","family":"Rossi","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro 21941590, Brazil"},{"name":"Clementino Fraga Filho University Hospiyal, Federal University of Rio de Janeiro, Rio de Janeiro 21941913, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7297-0781","authenticated-orcid":false,"given":"Rafael Soares","family":"Lindoso","sequence":"additional","affiliation":[{"name":"Carlos Chagas Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro 21941902, Brazil"},{"name":"National Center of Science and Technology for Regenerative Medicine\/REGENERA, Federal University of Rio de Janeiro, Rio de Janeiro 21941902, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1161\/CIRCULATIONAHA.110.963843","article-title":"Aspirin: A Historical and Contemporary Therapeutic Overview","volume":"123","author":"Fuster","year":"2011","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"220124","DOI":"10.1098\/rsob.220124","article-title":"Aspirin and Cancer: Biological Mechanisms and Clinical Outcomes","volume":"12","author":"Elwood","year":"2022","journal-title":"Open Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"12054","DOI":"10.1038\/s41598-022-16398-7","article-title":"Innovative Targets of the LncRNA-MiR-MRNA Network in Response to Low-Dose Aspirin in Breast Cancer Patients","volume":"12","author":"Alipour","year":"2022","journal-title":"Sci. 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