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Endoglin and MMP14 Contribute to Ewing Sarcoma Spreading by Modulation of Cell-Matrix Interactions.
Puerto-Camacho, Pilar; Díaz-Martín, Juan; Olmedo-Pelayo, Joaquín; Bolado-Carrancio, Alfonso; Salguero-Aranda, Carmen; Jordán-Pérez, Carmen; Esteban-Medina, Marina; Álamo-Álvarez, Inmaculada; Delgado-Bellido, Daniel; Lobo-Selma, Laura; Dopazo, Joaquín; Sastre, Ana; Alonso, Javier; Grünewald, Thomas G P; Bernabeu, Carmelo; Byron, Adam; Brunton, Valerie G; Amaral, Ana Teresa; de Álava, Enrique.
Afiliación
  • Puerto-Camacho P; Institute of Biomedicine of Sevilla (IBiS), Virgen del Rocio University Hospital/CSIC/University of Sevilla/CIBERONC, Molecular Pathology of Sarcomas, 41013 Seville, Spain.
  • Díaz-Martín J; Institute of Biomedicine of Sevilla (IBiS), Virgen del Rocio University Hospital/CSIC/University of Sevilla/CIBERONC, Molecular Pathology of Sarcomas, 41013 Seville, Spain.
  • Olmedo-Pelayo J; Department of Normal and Pathological Cytology and Histology, School of Medicine, University of Seville, 41009 Seville, Spain.
  • Bolado-Carrancio A; Institute of Biomedicine of Sevilla (IBiS), Virgen del Rocio University Hospital/CSIC/University of Sevilla/CIBERONC, Molecular Pathology of Sarcomas, 41013 Seville, Spain.
  • Salguero-Aranda C; Department of Normal and Pathological Cytology and Histology, School of Medicine, University of Seville, 41009 Seville, Spain.
  • Jordán-Pérez C; Cancer Research UK Edinburgh Centre, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh EH4 2XU, UK.
  • Esteban-Medina M; Institute of Biomedicine of Sevilla (IBiS), Virgen del Rocio University Hospital/CSIC/University of Sevilla/CIBERONC, Molecular Pathology of Sarcomas, 41013 Seville, Spain.
  • Álamo-Álvarez I; Department of Normal and Pathological Cytology and Histology, School of Medicine, University of Seville, 41009 Seville, Spain.
  • Delgado-Bellido D; Institute of Biomedicine of Sevilla (IBiS), Virgen del Rocio University Hospital/CSIC/University of Sevilla/CIBERONC, Molecular Pathology of Sarcomas, 41013 Seville, Spain.
  • Lobo-Selma L; Clinical Bioinformatics Area, Fundación Progreso y Salud (FPS), CDCA, Hospital Virgen del Rocío, 41013 Seville, Spain.
  • Dopazo J; Clinical Bioinformatics Area, Fundación Progreso y Salud (FPS), CDCA, Hospital Virgen del Rocío, 41013 Seville, Spain.
  • Sastre A; Institute of Biomedicine of Sevilla (IBiS), Virgen del Rocio University Hospital/CSIC/University of Sevilla/CIBERONC, Molecular Pathology of Sarcomas, 41013 Seville, Spain.
  • Alonso J; Institute of Biomedicine of Sevilla (IBiS), Virgen del Rocio University Hospital/CSIC/University of Sevilla/CIBERONC, Molecular Pathology of Sarcomas, 41013 Seville, Spain.
  • Grünewald TGP; Department of Normal and Pathological Cytology and Histology, School of Medicine, University of Seville, 41009 Seville, Spain.
  • Bernabeu C; Clinical Bioinformatics Area, Fundación Progreso y Salud (FPS), CDCA, Hospital Virgen del Rocío, 41013 Seville, Spain.
  • Byron A; Unidad Hemato-oncología Pediátrica, Hospital Infantil Universitario La Paz, 28046 Madrid, Spain.
  • Brunton VG; Unidad Hemato-oncología Pediátrica, Hospital Infantil Universitario La Paz, 28046 Madrid, Spain.
  • Amaral AT; Unidad de Tumores Sólidos Infantiles, Instituto de Investigación de Enfermedades Raras, Instituto de Salud Carlos III (IIER-ISCIII), 28029 Madrid, Spain.
  • de Álava E; Centro de Investigación Biomédica en Red de Enfermedades Raras, Instituto de Salud Carlos III (CB06/07/1009; CIBERER-ISCIII), 28029 Madrid, Spain.
Int J Mol Sci ; 23(15)2022 08 04.
Article en En | MEDLINE | ID: mdl-35955799
Endoglin (ENG) is a mesenchymal stem cell (MSC) marker typically expressed by active endothelium. This transmembrane glycoprotein is shed by matrix metalloproteinase 14 (MMP14). Our previous work demonstrated potent preclinical activity of first-in-class anti-ENG antibody-drug conjugates as a nascent strategy to eradicate Ewing sarcoma (ES), a devastating rare bone/soft tissue cancer with a putative MSC origin. We also defined a correlation between ENG and MMP14 expression in ES. Herein, we show that ENG expression is significantly associated with a dismal prognosis in a large cohort of ES patients. Moreover, both ENG/MMP14 are frequently expressed in primary ES tumors and metastasis. To deepen in their functional relevance in ES, we conducted transcriptomic and proteomic profiling of in vitro ES models that unveiled a key role of ENG and MMP14 in cell mechano-transduction. Migration and adhesion assays confirmed that loss of ENG disrupts actin filament assembly and filopodia formation, with a concomitant effect on cell spreading. Furthermore, we observed that ENG regulates cell-matrix interaction through activation of focal adhesion signaling and protein kinase C expression. In turn, loss of MMP14 contributed to a more adhesive phenotype of ES cells by modulating the transcriptional extracellular matrix dynamics. Overall, these results suggest that ENG and MMP14 exert a significant role in mediating correct spreading machinery of ES cells, impacting the aggressiveness of the disease.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Sarcoma de Ewing / Neoplasias Óseas / Endoglina Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Int J Mol Sci Año: 2022 Tipo del documento: Article País de afiliación: España Pais de publicación: Suiza
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Sarcoma de Ewing / Neoplasias Óseas / Endoglina Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Int J Mol Sci Año: 2022 Tipo del documento: Article País de afiliación: España Pais de publicación: Suiza