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Matrix metalloproteinase-9 induces a pro-angiogenic profile in chronic lymphocytic leukemia cells.
Aguilera-Montilla, Noemí; Bailón, Elvira; Ugarte-Berzal, Estefanía; Uceda-Castro, Rebeca; Prieto-Solano, María; García-Martínez, Elena; Samaniego, Rafael; Van den Steen, Philippe E; Opdenakker, Ghislain; García-Marco, José A; García-Pardo, Angeles.
Afiliação
  • Aguilera-Montilla N; Department of Molecular Biomedicine, Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain.
  • Bailón E; Department of Molecular Biomedicine, Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain.
  • Ugarte-Berzal E; Rega Institute for Medical Research, Department of Microbiology, Immunology and Transplantation, KU Leuven, Belgium.
  • Uceda-Castro R; Department of Molecular Biomedicine, Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain.
  • Prieto-Solano M; Department of Molecular Biomedicine, Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain.
  • García-Martínez E; Immuno-oncology Laboratory, Confocal Microscopy Unit, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain.
  • Samaniego R; Immuno-oncology Laboratory, Confocal Microscopy Unit, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain.
  • Van den Steen PE; Rega Institute for Medical Research, Department of Microbiology, Immunology and Transplantation, KU Leuven, Belgium.
  • Opdenakker G; Rega Institute for Medical Research, Department of Microbiology, Immunology and Transplantation, KU Leuven, Belgium.
  • García-Marco JA; Hematology Department, Hospital Universitario Puerta de Hierro, Madrid, Spain.
  • García-Pardo A; Department of Molecular Biomedicine, Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain. Electronic address: agarciapardo@cib.csic.es.
Biochem Biophys Res Commun ; 520(1): 198-204, 2019 11 26.
Article em En | MEDLINE | ID: mdl-31585732
ABSTRACT
Increased angiogenesis is commonly observed in chronic lymphocytic leukemia (CLL) tissues in correlation with advanced disease. CLL cells express pro- and anti-angiogenic genes and acquire a pro-angiogenic pattern upon interaction with the microenvironment. Because MMP-9 (a microenvironment component) plays important roles in solid tumor angiogenesis, we have studied whether MMP-9 influenced the angiogenic pattern in CLL cells. Immunofluorescence analyses confirmed the presence of MMP-9 in CLL tissues. MMP-9 interaction with CLL cells increased their MMP-9 expression and secretion into the medium. Accordingly, the conditioned media of MMP-9-primed CLL cells significantly enhanced endothelial cell proliferation, compared to control cells. MMP-9 also increased VEGF and decreased TSP-1 and Ang-2 expression, all at the gene and protein level, inducing a pro-angiogenic pattern in CLL cells. Mechanistic analyses demonstrated that downregulation of the selected gene TSP-1 by MMP-9 involved α4ß1 integrin, Src kinase family activity and the STAT3 transcription factor. Regulation of angiogenic genes is a novel contribution of MMP-9 to CLL pathology.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Leucemia Linfocítica Crônica de Células B / Metaloproteinase 9 da Matriz / Angiopoietina-2 / Fator de Transcrição STAT3 / Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos / Neovascularização Patológica Limite: Aged / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2019 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Leucemia Linfocítica Crônica de Células B / Metaloproteinase 9 da Matriz / Angiopoietina-2 / Fator de Transcrição STAT3 / Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos / Neovascularização Patológica Limite: Aged / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2019 Tipo de documento: Article