|
rdf:type |
|
|
lifeskim:mentions |
umls-concept:C0023434,
umls-concept:C0037083,
umls-concept:C0165519,
umls-concept:C0521119,
umls-concept:C0600210,
umls-concept:C1314939,
umls-concept:C1332684,
umls-concept:C1413191,
umls-concept:C1704675,
umls-concept:C1710082,
umls-concept:C2699153
|
|
pubmed:issue |
1
|
|
pubmed:dateCreated |
2007-12-24
|
|
pubmed:abstractText |
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.
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
AIM
|
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/CCL21 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/CCR7 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Chemokine CCL21,
http://linkedlifedata.com/resource/pubmed/chemical/Collagen,
http://linkedlifedata.com/resource/pubmed/chemical/Drug Combinations,
http://linkedlifedata.com/resource/pubmed/chemical/Laminin,
http://linkedlifedata.com/resource/pubmed/chemical/Matrix Metalloproteinase 9,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Proteoglycans,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, CCR7,
http://linkedlifedata.com/resource/pubmed/chemical/matrigel
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Jan
|
|
pubmed:issn |
0006-4971
|
|
pubmed:author |
|
|
pubmed:issnType |
Print
|
|
pubmed:day |
1
|
|
pubmed:volume |
111
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
383-6
|
|
pubmed:dateRevised |
2009-11-19
|
|
pubmed:meshHeading |
pubmed-meshheading:17890452-Cell Movement,
pubmed-meshheading:17890452-Chemokine CCL21,
pubmed-meshheading:17890452-Collagen,
pubmed-meshheading:17890452-Drug Combinations,
pubmed-meshheading:17890452-Endothelium, Vascular,
pubmed-meshheading:17890452-Humans,
pubmed-meshheading:17890452-Laminin,
pubmed-meshheading:17890452-Leukemia, Lymphocytic, Chronic, B-Cell,
pubmed-meshheading:17890452-MAP Kinase Signaling System,
pubmed-meshheading:17890452-Matrix Metalloproteinase 9,
pubmed-meshheading:17890452-Mitogen-Activated Protein Kinase 1,
pubmed-meshheading:17890452-Mitogen-Activated Protein Kinase 3,
pubmed-meshheading:17890452-Neoplasm Invasiveness,
pubmed-meshheading:17890452-Proteoglycans,
pubmed-meshheading:17890452-Receptors, CCR7,
pubmed-meshheading:17890452-Tumor Cells, Cultured,
pubmed-meshheading:17890452-Umbilical Veins,
pubmed-meshheading:17890452-Up-Regulation
|
|
pubmed:year |
2008
|
|
pubmed:articleTitle |
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.
|
|
pubmed:affiliation |
Departamento de Fisiopatología Celular y Molecular, Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas (CSIC), Madrid.
|
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|
