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In breast cancer, EVs released by malignant cells carry bioactive molecules capable of altering the behaviour of surrounding cells. However, it remains uncertain whether these vesicles can directly induce a more aggressive phenotype in benign mammary cells. Melatonin, known for its oncostatic properties, regulates proliferation, metabolism, and signalling pathways associated with tumour progression and may modulate EV\u2010mediated intercellular communication. This study evaluated whether EVs derived from four breast cancer cell lines (MCF\u20107, MDA\u2010MB\u2010231, MDA\u2010MB\u2010453 and HCC70), treated or not with melatonin, can modify the phenotype of benign MCF10A cells. EVs were isolated from conditioned media and co\u2010cultured with benign cells. Assays of proliferation, viability, colony formation, migration, lactate production and immunofluorescence were performed to assess EV\u2010mediated effects. EVs derived from malignant cells promoted a more aggressive phenotype in benign cells, as evidenced by increased proliferation, migration, and phenotypic remodelling. In contrast, EVs derived from melatonin\u2010treated malignant cells were associated with reduced lactate production and attenuation of pro\u2010tumoural features. Overall, these findings demonstrate that tumour\u2010derived EVs can induce aggressive traits in benign mammary cells and suggest that melatonin exposure in donor cells modulates EV\u2010mediated effects, attenuating their pro\u2010tumoural influence.<\/jats:p>","DOI":"10.1111\/jcmm.71309","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T04:21:52Z","timestamp":1786508512000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Novel Mechanism of Tumour Communication: Malignant Extracellular Vesicles\u2010Induced Aggressiveness in Benign Cells and Melatonin\u2010Driven Reversal"],"prefix":"10.1111","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6275-3273","authenticated-orcid":false,"given":"Barbara Maria","family":"Frigieri","sequence":"first","affiliation":[{"name":"Cancer Molecular Research Laboratory (CMRL), Faculdade de Medicina de S\u00e3o Jos\u00e9 do Rio 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