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Blood, 1 January 2008, Vol. 111, No. 1, pp. 383-386. Prepublished online as a Blood First Edition Paper on September 21, 2007; DOI 10.1182/blood-2007-08-107300. This Article Full Text Full Text (PDF) Supplemental Methods and Figure All Versions of this Article: blood-2007-08-107300v1 111/1/383    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Redondo-Muñoz, J. Articles by García-Pardo, A. Search for Related Content PubMed PubMed Citation Articles by Redondo-Muñoz, J. Articles by García-Pardo, A. Related Collections Neoplasia Cell Adhesion and Motility Signal Transduction Gene Expression Brief Reports Chemokines, Cytokines, and Interleukins Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Brief Report Matrix metalloproteinase-9 is up-regulated by CCL21/CCR7 interaction via extracellular signal-regulated kinase-1/2 signaling and is involved in CCL21-driven B-cell chronic lymphocytic leukemia cell invasion and migration Javier Redondo-Muñoz1, María José Terol2, José A. García-Marco3, and Angeles García-Pardo1 1 Departamento de Fisiopatología Celular y Molecular, Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas (CSIC), Madrid; 2 Servicio de Hematología y Medicina Oncológica, Hospital Clínico, Valencia; and 3 Servicio de Hematología, Hospital Puerta de Hierro, Madrid, Spain B-cell chronic lymphocytic leukemia (B-CLL) progression is frequently accompanied by clinical lymphadenopathy, and the CCL21 chemokine may play an important role in this process. Indeed, CCR7 (the CCL21 receptor), as well as matrix metalloproteinase-9 (MMP-9), are overexpressed in infiltrating B-CLL cells. We have studied whether MMP-9 is regulated by CCL21 and participates in CCL21-dependent migration. CCL21 significantly increased B-CLL MMP-9 production, measured by gelatin zymography. This was inhibited by blocking extracellular signal-regulated kinase-1/2 (ERK1/2) activity or by cell transfection with CCR7-siRNA. Accordingly, CCL21/CCR7 interaction activated the ERK1/2/c-Fos pathway and increased MMP-9 mRNA. CCL21-driven B-CLL cell migration through Matrigel or human umbilical vein endothelial cells (HUVEC) was blocked by anti-CCR7 antibodies, CCR7-siRNA transfection, or the ERK1/2 inhibitor U0126, as well as by anti-MMP-9 antibodies or tissue inhibitor of metalloproteinase 1 (TIMP-1). These results strongly suggest that MMP-9 is involved in B-CLL nodal infiltration and expand the roles of MMP-9 and CCR7 in B-CLL progression. Both molecules could thus constitute therapeutic targets for this disease. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. Redondo-Munoz, E. Ugarte-Berzal, J. A. Garcia-Marco, M. H. del Cerro, P. E. Van den Steen, G. Opdenakker, M. J. Terol, and A. Garcia-Pardo {alpha}4{beta}1 integrin and 190-kDa CD44v constitute a cell surface docking complex for gelatinase B/MMP-9 in chronic leukemic but not in normal B cells Blood, July 1, 2008; 112(1): 169 - 178. [Abstract] [Full Text] [PDF]

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