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Blood, 1 July 2008, Vol. 112, No. 1, pp. 169-178. Prepublished online as a Blood First Edition Paper on March 7, 2008; DOI 10.1182/blood-2007-08-109249. This Article Full Text (PDF) Supplemental Methods and Figures All Versions of this Article: blood-2007-08-109249v1 112/1/169    most recent Alert me when this article is cited Alert me if a correction is posted 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-Munoz, J. Articles by Garcia-Pardo, A. Search for Related Content PubMed PubMed Citation Articles by Redondo-Munoz, J. Articles by Garcia-Pardo, A. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted August 24, 2007 Accepted March 5, 2008 41 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 Javier Redondo-Munoz, Estefania Ugarte-Berzal, Jose A Garcia-Marco, Mercedes Hernandez del Cerro, Philippe E. Van den Steen, Ghislain Opdenakker, Maria Jose Terol, and Angeles Garcia-Pardo* Departamento de Fisiopatologia Celular y Molecular, Centro de Investigaciones Biologicas, Consejo Superior de Investigaciones Cientificas, Madrid, Spain Servicio de Hematologia, Hospital Puerta de Hierro, Madrid, Spain Rega Institute for Medical Research, University of Leuven, Leuven, Belgium Servicio de Hematologia y Medicina Oncologica, Hospital Clinico, Valencia, Spain * Corresponding author; email: agarciapardo{at}cib.csic.es. As B-cell chronic lymphocytic leukemia (B-CLL) progresses, malignant cells extravasate and infiltrate lymphoid tissues. Several molecules, including gelatinase B/MMP-9, contribute to these processes. Although mainly a secreted protease, some MMP-9 is present at the B-CLL cell surface and the function, mode of anchoring and interactions of this MMP-9 are unknown. Here we show that anti-MMP-9 antibodies immunoprecipitated a 190 kDa CD44v isoform and 41 integrin from B-CLL cells, but not from normal B cells. Function-blocking antibodies to 41 or CD44 or transfection with specific siRNAs, decreased cell-associated proMMP-9 and increased the secreted form. B-CLL cells attached to and bound pro- and active MMP-9 and this was inhibited by blocking the expression or function of 41 or CD44. The MMP-9 hemopexin domain was critical in these interactions. 41 and 190 kDa CD44v (but not CD44H) formed a complex at the cell surface, since they both co-immunoprecipitated with anti-4, anti-1 or anti-CD44 antibodies. Immunofluorescence analyses confirmed that 41 and CD44v colocalized with MMP-9. Binding of proMMP-9 inhibited B-CLL cell migration and this required MMP-9 proteolytic activity. Thus, we have identified 41 and CD44v as a novel proMMP-9 cell surface docking complex and we show that cell-associated MMP-9 may regulate B-CLL cell migration and arrest. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Gang of 3 in aggressive CLL? Grzegorz S. Nowakowski Blood 2008 112: 5-6. [Full Text] [PDF] This article has been cited by other articles: J. A. Burger, P. Ghia, A. Rosenwald, and F. Caligaris-Cappio The microenvironment in mature B-cell malignancies: a target for new treatment strategies Blood, October 15, 2009; 114(16): 3367 - 3375. [Abstract] [Full Text] [PDF] M. Stefanidakis, K. Karjalainen, D. E. Jaalouk, C. G. Gahmberg, S. O'Brien, R. Pasqualini, W. Arap, and E. Koivunen Role of leukemia cell invadosome in extramedullary infiltration Blood, October 1, 2009; 114(14): 3008 - 3017. [Abstract] [Full Text] [PDF] V. C. Ardi, P. E. Van den Steen, G. Opdenakker, B. Schweighofer, E. I. Deryugina, and J. P. Quigley Neutrophil MMP-9 Proenzyme, Unencumbered by TIMP-1, Undergoes Efficient Activation in Vivo and Catalytically Induces Angiogenesis via a Basic Fibroblast Growth Factor (FGF-2)/FGFR-2 Pathway J. Biol. Chem., September 18, 2009; 284(38): 25854 - 25866. [Abstract] [Full Text] [PDF] J. E. Adair, V. Stober, M. Sobhany, L. Zhuo, J. D. Roberts, M. Negishi, K. Kimata, and S. Garantziotis Inter-{alpha}-trypsin Inhibitor Promotes Bronchial Epithelial Repair after Injury through Vitronectin Binding J. Biol. Chem., June 19, 2009; 284(25): 16922 - 16930. [Abstract] [Full Text] [PDF] S. Deaglio and F. Malavasi Chronic lymphocytic leukemia microenvironment: shifting the balance from apoptosis to proliferation Haematologica, June 1, 2009; 94(6): 752 - 756. [Full Text] [PDF]

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