Small Extracellular Vesicles from Hypoxic Triple-Negative Breast Cancer Cells Induce Oxygen-Dependent Cell Invasion

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dc.contributor.authorPachane, Bianca Cruz
dc.contributor.authorNunes, Ana Carolina Caetano
dc.contributor.authorCataldi, Thais Regiani
dc.contributor.authorMicocci, Kelli Cristina [UNESP]
dc.contributor.authorMoreira, Bianca Caruso
dc.contributor.authorLabate, Carlos Alberto
dc.contributor.authorSelistre-de-Araujo, Heloisa Sobreiro
dc.contributor.authorAltei, Wanessa Fernanda
dc.contributor.institutionUniversidade Federal de São Carlos (UFSCar)
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.contributor.institutionUniversidade Estadual Paulista (UNESP)
dc.contributor.institutionBarretos Cancer Hospital
dc.date.accessioned2023-07-29T13:26:46Z
dc.date.available2023-07-29T13:26:46Z
dc.date.issued2022-10-01
dc.description.abstractHypoxia, a condition of low oxygenation frequently found in triple-negative breast tumors (TNBC), promotes extracellular vesicle (EV) secretion and favors cell invasion, a complex process in which cell morphology is altered, dynamic focal adhesion spots are created, and ECM is remodeled. Here, we investigated the invasive properties triggered by TNBC-derived hypoxic small EV (SEVh) in vitro in cells cultured under hypoxic (1% O2) and normoxic (20% O2) conditions, using phenotypical and proteomic approaches. SEVh characterization demonstrated increased protein abundance and diversity over normoxic SEV (SEVn), with enrichment in pro-invasive pathways. In normoxic cells, SEVh promotes invasive behavior through pro-migratory morphology, invadopodia development, ECM degradation, and matrix metalloprotease (MMP) secretion. The proteome profiling of 20% O2-cultured cells exposed to SEVh determined enrichment in metabolic processes and cell cycles, modulating cell health to escape apoptotic pathways. In hypoxia, SEVh was responsible for proteolytic and catabolic pathway inducement, interfering with integrin availability and gelatinase expression. Overall, our results demonstrate the importance of hypoxic signaling via SEV in tumors for the early establishment of metastasis.en
dc.description.affiliationBiochemistry and Molecular Biology Laboratory Department of Physiological Sciences Universidade Federal de São Carlos—UFSCar, SP
dc.description.affiliationMax Feffer Plant Genetics Laboratory Department of Genetics University of São Paulo—ESALQ, SP
dc.description.affiliationCenter for the Study of Social Insects São Paulo State University “Julio de Mesquita Filho”, SP
dc.description.affiliationMolecular Oncology Research Center Barretos Cancer Hospital, SP
dc.description.affiliationRadiation Oncology Department Barretos Cancer Hospital, SP
dc.description.affiliationUnespCenter for the Study of Social Insects São Paulo State University “Julio de Mesquita Filho”, SP
dc.identifierhttp://dx.doi.org/10.3390/ijms232012646
dc.identifier.citationInternational Journal of Molecular Sciences, v. 23, n. 20, 2022.
dc.identifier.doi10.3390/ijms232012646
dc.identifier.issn1422-0067
dc.identifier.issn1661-6596
dc.identifier.scopus2-s2.0-85140980595
dc.identifier.urihttp://hdl.handle.net/11449/247820
dc.language.isoeng
dc.relation.ispartofInternational Journal of Molecular Sciences
dc.sourceScopus
dc.subjectbreast cancer
dc.subjectcell invasion
dc.subjectextracellular vesicles
dc.subjecthypoxia
dc.titleSmall Extracellular Vesicles from Hypoxic Triple-Negative Breast Cancer Cells Induce Oxygen-Dependent Cell Invasionen
dc.typeArtigo
unesp.author.orcid0000-0002-7302-4498[1]
unesp.author.orcid0000-0002-8213-2159[2]
unesp.author.orcid0000-0002-9827-2017[3]
unesp.author.orcid0000-0002-8694-885X[5]
unesp.author.orcid0000-0002-6636-7951[8]

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