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Extracellular vesicles from thyroid cancer harbor a functional machinery involved in extracellular matrix remodeling.
Bravo-Miana, Rocío Del Carmen; Soler, María Florencia; Ceschin, Danilo Guillermo; Royo, Félix; Negretti-Borga, Dana María; Azkargorta, Mikel; Elortza, Félix; Montesinos, María Del Mar; Pellizas, Claudia Gabriela; Falcón-Pérez, Juan Manuel; Donadio, Ana Carolina.
Afiliação
  • Bravo-Miana RDC; Universidad Nacional de Córdoba, Facultad de Ciencias Químicas, Departamento de Bioquímica Clínica, Córdoba, Argentina; Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI-CONICET), Ciudad Universitaria, Haya de la Torre y Medina Allende, Córdoba X5000HUA, Argentina.
  • Soler MF; Universidad Nacional de Córdoba, Facultad de Ciencias Químicas, Departamento de Bioquímica Clínica, Córdoba, Argentina; Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI-CONICET), Ciudad Universitaria, Haya de la Torre y Medina Allende, Córdoba X5000HUA, Argentina.
  • Ceschin DG; Centro de Investigación en Medicina Traslacional Severo Amuchástegui, Instituto Universitario de Ciencias Biomédicas de Córdoba, Naciones Unidas 420, Parque Velez Sarsfield, Córdoba, Argentina.
  • Royo F; Exosomes Laboratory, CIC bioGUNE-BRTA, CIBERehd, Bizkaia Technology Park, Derio 48160, Spain.
  • Negretti-Borga DM; Universidad Nacional de Córdoba, Facultad de Ciencias Químicas, Departamento de Bioquímica Clínica, Córdoba, Argentina; Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI-CONICET), Ciudad Universitaria, Haya de la Torre y Medina Allende, Córdoba X5000HUA, Argentina.
  • Azkargorta M; Proteomics Unit, CICbioGUNE-BRTA, CIBERehd, ProteoRed, Bizkaia Technology Park, Derio 48160, Bizkaia, Spain.
  • Elortza F; Proteomics Unit, CICbioGUNE-BRTA, CIBERehd, ProteoRed, Bizkaia Technology Park, Derio 48160, Bizkaia, Spain.
  • Montesinos MDM; Universidad Nacional de Córdoba, Facultad de Ciencias Químicas, Departamento de Bioquímica Clínica, Córdoba, Argentina; Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI-CONICET), Ciudad Universitaria, Haya de la Torre y Medina Allende, Córdoba X5000HUA, Argentina.
  • Pellizas CG; Universidad Nacional de Córdoba, Facultad de Ciencias Químicas, Departamento de Bioquímica Clínica, Córdoba, Argentina; Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI-CONICET), Ciudad Universitaria, Haya de la Torre y Medina Allende, Córdoba X5000HUA, Argentina.
  • Falcón-Pérez JM; Exosomes Laboratory, CIC bioGUNE-BRTA, CIBERehd, Bizkaia Technology Park, Derio 48160, Spain; IKERBASQUE, Basque Foundation for Science, 48013 Bilbao, Spain. Electronic address: jfalcon@cicbiogune.es.
  • Donadio AC; Universidad Nacional de Córdoba, Facultad de Ciencias Químicas, Departamento de Bioquímica Clínica, Córdoba, Argentina; Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI-CONICET), Ciudad Universitaria, Haya de la Torre y Medina Allende, Córdoba X5000HUA, Argentina. Electronic add
Eur J Cell Biol ; 101(3): 151254, 2022.
Article em En | MEDLINE | ID: mdl-35849996
Extracellular vesicles (EVs) participate in cell-stroma crosstalk within the tumor microenvironment and fibroblasts (Fb) contribute to tumor promotion in thyroid cancer. However, the role of tumor-stroma derived EVs still needs to be deciphered. We hypothesized that the interaction of thyroid tumor cells with Fb would liberate EVs with a specific proteomic profile, which would have an impact on EV-functionality in thyroid tumor progression-related events. Tumor (TPC-1, 8505c) and non-tumor (NThyOri) thyroid cells were co-cultured with human Fb. EVs, obtained by ultracentrifugation of conditioned media, were characterized by nanoparticle tracking analysis and western blotting. EV-proteomic analysis was performed by mass-spectrometry, and metalloproteinases (MMPs) were studied by zymography. EV-exchange was evaluated using immunofluorescence, confocal microscopy and FACS. EVs expressed classical exosome markers, with EVs from thyroid tumor cell-Fb co-cultures showing a proteomic profile related to extracellular matrix (ECM) remodeling. Bidirectional crosstalk between Fb and TPC-1 cells produced significantly more EVs than their isolated cells, and potentiated EV-functionality. In line with this, Fb-TPC-1 derived EVs induced MMP2 activation in NThyOri supernatants, and MMP2 activity could be evidenced in Fb and TPC-1 contact-independent co-cultures. Besides, MMP2 interactors allowed us to discriminate between EVs from thyroid tumoral and non-tumoral milieus. Interestingly, Fb internalized more EVs from TPC-1 than from NThyOri producing cells. Fb and thyroid tumor cell crosstalk produces specialized EVs with an ECM remodeling proteomic profile, enabling activation of MMP2 and possibly facilitating ECM-degradation, which is potentially linked with thyroid tumor progression.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Glândula Tireoide / Vesículas Extracelulares Limite: Humans Idioma: En Revista: Eur J Cell Biol Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Argentina País de publicação: Alemanha
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Glândula Tireoide / Vesículas Extracelulares Limite: Humans Idioma: En Revista: Eur J Cell Biol Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Argentina País de publicação: Alemanha