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The cancer-related transcription factor RUNX2 modulates expression and secretion of the matricellular protein osteopontin in osteosarcoma cells to promote adhesion to endothelial pulmonary cells and lung metastasis.
Villanueva, Francisco; Araya, Hector; Briceño, Pedro; Varela, Nelson; Stevenson, Andres; Jerez, Sofia; Tempio, Fabian; Chnaiderman, Jonas; Perez, Carola; Villarroel, Milena; Concha, Emma; Khani, Farzaneh; Thaler, Roman; Salazar-Onfray, Flavio; Stein, Gary S; van Wijnen, Andre J; Galindo, Mario.
Afiliación
  • Villanueva F; Millennium Institute on Immunology and Immunotherapy, University of Chile, Santiago, Chile.
  • Araya H; Program of Cellular and Molecular Biology, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile.
  • Briceño P; Millennium Institute on Immunology and Immunotherapy, University of Chile, Santiago, Chile.
  • Varela N; Program of Cellular and Molecular Biology, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile.
  • Stevenson A; Millennium Institute on Immunology and Immunotherapy, University of Chile, Santiago, Chile.
  • Jerez S; Program of Cellular and Molecular Biology, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile.
  • Tempio F; Millennium Institute on Immunology and Immunotherapy, University of Chile, Santiago, Chile.
  • Chnaiderman J; Department of Medical Technology, Faculty of Medicine, University of Chile, Santiago, Chile.
  • Perez C; Millennium Institute on Immunology and Immunotherapy, University of Chile, Santiago, Chile.
  • Villarroel M; Program of Cellular and Molecular Biology, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile.
  • Concha E; Millennium Institute on Immunology and Immunotherapy, University of Chile, Santiago, Chile.
  • Khani F; Program of Cellular and Molecular Biology, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile.
  • Thaler R; Millennium Institute on Immunology and Immunotherapy, University of Chile, Santiago, Chile.
  • Salazar-Onfray F; Program of Immunology, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile.
  • Stein GS; Program of Virology, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile.
  • van Wijnen AJ; Laboratory Animal Facility, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile.
  • Galindo M; Department of Oncology, Hospital Dr. Luis Calvo Mackenna, Santiago, Chile.
J Cell Physiol ; 234(8): 13659-13679, 2019 08.
Article en En | MEDLINE | ID: mdl-30637720
Osteosarcomas are bone tumors that frequently metastasize to the lung. Aberrant expression of the transcription factor, runt-related transcription factor 2 (RUNX2), is a key pathological feature in osteosarcoma and associated with loss of p53 and miR-34 expression. Elevated RUNX2 may transcriptionally activate genes mediating tumor progression and metastasis, including the RUNX2 target gene osteopontin (OPN/SPP1). This gene encodes a secreted matricellular protein produced by osteoblasts to regulate bone matrix remodeling and tissue calcification. Here we investigated whether and how the RUNX2/OPN axis regulates lung metastasis of osteosarcoma. Importantly, RUNX2 depletion attenuates lung metastasis of osteosarcoma cells in vivo. Using next-generation RNA-sequencing, protein-based assays, as well as the loss- and gain-of-function approaches in selected osteosarcoma cell lines, we show that osteopontin messenger RNA levels closely correlate with RUNX2 expression and that RUNX2 controls the levels of secreted osteopontin. Elevated osteopontin levels promote heterotypic cell-cell adhesion of osteosarcoma cells to human pulmonary microvascular endothelial cells, but not in the presence of neutralizing antibodies. Collectively, these findings indicate that the RUNX2/OPN axis regulates the ability of osteosarcoma cells to attach to pulmonary endothelial cells as a key step in metastasis of osteosarcoma cells to the lung.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Óseas / Osteosarcoma / Regulación Neoplásica de la Expresión Génica / Subunidad alfa 1 del Factor de Unión al Sitio Principal / Osteopontina / Invasividad Neoplásica Límite: Animals / Humans Idioma: En Revista: J Cell Physiol Año: 2019 Tipo del documento: Article País de afiliación: Chile Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Óseas / Osteosarcoma / Regulación Neoplásica de la Expresión Génica / Subunidad alfa 1 del Factor de Unión al Sitio Principal / Osteopontina / Invasividad Neoplásica Límite: Animals / Humans Idioma: En Revista: J Cell Physiol Año: 2019 Tipo del documento: Article País de afiliación: Chile Pais de publicación: Estados Unidos