Extracellular Signaling Molecules from Adipose-Derived Stem Cells and Ovarian Cancer Cells Induce a Hybrid Epithelial-Mesenchymal Phenotype in a Bidirectional Interaction

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Autor(es): dc.contributorUniversidade Estadual Paulista (UNESP)-
Autor(es): dc.contributorUniversidade de São Paulo (USP)-
Autor(es): dc.contributorFaculty of Medicine of São José do Rio Preto (Famerp)-
Autor(es): dc.contributorUT Health-
Autor(es): dc.creatorSimão, Vinícius Augusto-
Autor(es): dc.creatorFloriano, Juliana Ferreira-
Autor(es): dc.creatorCesário, Roberta Carvalho-
Autor(es): dc.creatorTonon, Karolina da Silva-
Autor(es): dc.creatorde Oliveira, Larissa Ragozo Cardoso-
Autor(es): dc.creatorDelella, Flávia Karina-
Autor(es): dc.creatorAlmeida, Fausto-
Autor(es): dc.creatorSantos, Lucilene Delazari dos-
Autor(es): dc.creatorSeiva, Fábio Rodrigues Ferreira-
Autor(es): dc.creatorde Campos Zuccari, Débora Aparecida Pires-
Autor(es): dc.creatorRibeiro-Paes, João Tadeu-
Autor(es): dc.creatorReiter, Russel J.-
Autor(es): dc.creatorde Almeida Chuffa, Luiz Gustavo-
Data de aceite: dc.date.accessioned2025-08-21T16:30:48Z-
Data de disponibilização: dc.date.available2025-08-21T16:30:48Z-
Data de envio: dc.date.issued2025-04-29-
Data de envio: dc.date.issued2025-03-01-
Fonte completa do material: dc.identifierhttp://dx.doi.org/10.3390/cells14050374-
Fonte completa do material: dc.identifierhttps://hdl.handle.net/11449/299046-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/11449/299046-
Descrição: dc.descriptionOvarian cancer (OC) is characterized by high mortality rates due to late diagnosis, recurrence, and metastasis. Here, we show that extracellular signaling molecules secreted by adipose-derived mesenchymal stem cells (ASCs) and OC cells—either in the conditioned medium (CM) or within small extracellular vesicles (sEVs)—modulate cellular responses and drive OC progression. ASC-derived sEVs and CM secretome promoted OC cell colony formation, invasion, and migration while upregulating tumor-associated signaling pathways, including TGFβ/Smad, p38MAPK/ERK1/2, Wnt/β-catenin, and MMP-9. Additionally, OC-derived sEVs and CM induced a pro-tumorigenic phenotype in ASCs, enhancing their invasiveness and expression of tumor-associated factors. Notably, both ASCs and OC cells exhibited increased expression of E-cadherin and Snail/Slug proteins, key markers of epithelial/mesenchymal hybrid phenotype, enhancing cellular plasticity and metastatic potential. We also demonstrated that these cellular features are, at least in part, due to the presence of tumor-supportive molecules such as TNF-α, Tenascin-C, MMP-2, and SDF-1α in the CM secretome of ASCs and OC cells. In silico analyses linked these molecular changes to poor prognostic outcomes in OC patients. These findings highlight the critical role of sEVs and tumor/stem cell-derived secretome in OC progression through bidirectional interactions that impact cellular behavior and phenotypic transitions. We suggest that targeting EV-mediated communication could improve therapeutic strategies and patient outcomes.-
Descrição: dc.descriptionDepartment of Structural and Functional Biology Institute of Biosciences São Paulo State University (Unesp), Botucatu 18618-689-
Descrição: dc.descriptionBioengineering & Biomaterials Group School of Pharmaceutical Sciences São Paulo State University (Unesp), Km 01 Araraquara-Jaú RoadSão Paulo-
Descrição: dc.descriptionDepartment of Biochemistry and Immunology Ribeirao Preto Medical School University of São Paulo (Usp), Ribeirão Preto-
Descrição: dc.descriptionInstitute for Biotechnology São Paulo State University (Unesp), Botucatu 18607-440-
Descrição: dc.descriptionDepartment of Chemistry and Biochemistry Institute of Biosciences São Paulo State University (Unesp), São Paulo-
Descrição: dc.descriptionDepartment of Molecular Biology Faculty of Medicine of São José do Rio Preto (Famerp), São José do Rio Preto 15090-000-
Descrição: dc.descriptionDepartment of Biotechnology School of Sciences Humanities and Languages São Paulo State University (Unesp), São Paulo-
Descrição: dc.descriptionDepartment of Cell Systems and Anatomy UT Health-
Descrição: dc.descriptionDepartment of Structural and Functional Biology Institute of Biosciences São Paulo State University (Unesp), Botucatu 18618-689-
Descrição: dc.descriptionBioengineering & Biomaterials Group School of Pharmaceutical Sciences São Paulo State University (Unesp), Km 01 Araraquara-Jaú RoadSão Paulo-
Descrição: dc.descriptionInstitute for Biotechnology São Paulo State University (Unesp), Botucatu 18607-440-
Descrição: dc.descriptionDepartment of Chemistry and Biochemistry Institute of Biosciences São Paulo State University (Unesp), São Paulo-
Descrição: dc.descriptionDepartment of Biotechnology School of Sciences Humanities and Languages São Paulo State University (Unesp), São Paulo-
Idioma: dc.languageen-
Relação: dc.relationCells-
???dc.source???: dc.sourceScopus-
Palavras-chave: dc.subjectadipose-derived mesenchymal stem cells-
Palavras-chave: dc.subjectcell invasion and migration-
Palavras-chave: dc.subjectconditioned medium-
Palavras-chave: dc.subjectexosome-
Palavras-chave: dc.subjectindirect co-culture-
Palavras-chave: dc.subjectmetastable phenotype-
Palavras-chave: dc.subjectOVCAR3-
Palavras-chave: dc.subjectsecretome-
Palavras-chave: dc.subjectSKOV3-
Palavras-chave: dc.subjectsmall extracellular vesicles-
Título: dc.titleExtracellular Signaling Molecules from Adipose-Derived Stem Cells and Ovarian Cancer Cells Induce a Hybrid Epithelial-Mesenchymal Phenotype in a Bidirectional Interaction-
Tipo de arquivo: dc.typelivro digital-
Aparece nas coleções:Repositório Institucional - Unesp

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