| Autor: |
Pachane BC; Biochemistry and Molecular Biology Laboratory, Department of Physiological Sciences, Universidade Federal de São Carlos-UFSCar, São Carlos 13565-905, SP, Brazil., Nunes ACC; Biochemistry and Molecular Biology Laboratory, Department of Physiological Sciences, Universidade Federal de São Carlos-UFSCar, São Carlos 13565-905, SP, Brazil., Cataldi TR; Max Feffer Plant Genetics Laboratory, Department of Genetics, University of São Paulo-ESALQ, Piracicaba 13418-900, SP, Brazil., Micocci KC; Center for the Study of Social Insects, São Paulo State University 'Julio de Mesquita Filho', Rio Claro 14884-900, SP, Brazil., Moreira BC; Biochemistry and Molecular Biology Laboratory, Department of Physiological Sciences, Universidade Federal de São Carlos-UFSCar, São Carlos 13565-905, SP, Brazil., Labate CA; Max Feffer Plant Genetics Laboratory, Department of Genetics, University of São Paulo-ESALQ, Piracicaba 13418-900, SP, Brazil., Selistre-de-Araujo HS; Biochemistry and Molecular Biology Laboratory, Department of Physiological Sciences, Universidade Federal de São Carlos-UFSCar, São Carlos 13565-905, SP, Brazil., Altei WF; Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos 14784-400, SP, Brazil.; Radiation Oncology Department, Barretos Cancer Hospital, Barretos 14784-400, SP, Brazil. |
| Abstrakt: |
Hypoxia, 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% O 2 ) and normoxic (20% O 2 ) 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% O 2 -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. |
