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Blood, 15 February 2005, Vol. 105, No. 4, pp. 1660-1668. Prepublished online as a Blood First Edition Paper on October 12, 2004; DOI 10.1182/blood-2004-04-1385. This Article Full Text Full Text (PDF) Erratum (v105,p3000) All Versions of this Article: 2004-04-1385v1 105/4/1660    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 Guedez, L. Articles by Stetler-Stevenson, W. G. Search for Related Content PubMed PubMed Citation Articles by Guedez, L. Articles by Stetler-Stevenson, W. G. Related Collections Hemostasis, Thrombosis, and Vascular Biology Neoplasia Oncogenes and Tumor Suppressors Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Tissue inhibitor of metalloproteinase 1 (TIMP-1) promotes plasmablastic differentiation of a Burkitt lymphoma cell line: implications in the pathogenesis of plasmacytic/plasmablastic tumors Liliana Guedez, Antonio Martinez, Shumei Zhao, Angelica Vivero, Stefania Pittaluga, Maryalice Stetler-Stevenson, Mark Raffeld, and William G. Stetler-Stevenson From the Cell and Cancer Biology Branch and Hematopathology Section, Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, Bethesda, MD; and Department of Pathology, Hospital del Mar, Barcelona, Spain. Tissue inhibitor of metalloproteinase 1 (TIMP-1) is a stromal factor with multiple functions. Overexpression of TIMP-1 correlates with aggressive clinical behavior of a spectrum of tumors. Here, for the first time, we address the role of TIMP-1 in the pathogenesis of B-cell lymphomas. An Epstein-Barr virus (EBV)-negative Burkitt lymphoma cell line with ectopic TIMP-1 expression (TIMP-1JD38) was used to identify genes induced/repressed by TIMP-1. Differentially expressed genes were analyzed by cDNA microarray, and they were validated by immunohistochemistry, flow cytometry, and Western blotting. Analysis revealed changes of genes coding for B-cell growth/differentiation, transcription, and cell cycle regulators. TIMP-1 repressed expression of germinal center (GC) markers CD10, Bcl-6, PAX-5 and up-regulated plasma cell-associated antigens CD138, MUM-1/IRF-4, XBP-1, and CD44, suggesting a plasma cell differentiation. This is accompanied by activation of signal transducer and activator of transcription 3 (STAT-3) and switch to cyclin D2 expression. However, TIMP-1JD38 cells expressed an inactive form of XBP-1, lacking antibody production/secretion. This incomplete plasmacytic differentiation occurs without altering cell proliferation, and despite c-Myc deregulation, indicating an arrested plasmacytic/plasmablastic stage of differentiation. Further validation in human lymphoma cell lines and in primary B-cell tumors demonstrated a predominant TIMP-1 expression in tumors with plasmacytic/plasmablastic phenotypes, including multiple myelomas. These findings strongly support TIMP-1 as an important factor in the pathogenesis of plasmacytic/plasmablastic tumors. (Blood. 2005;105:1660-1668) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. Dien, H. M. Amin, N. Chiu, W. Wong, C. Frantz, B. Chiu, J. R. Mackey, and R. Lai Signal Transducers and Activators of Transcription-3 Up-Regulates Tissue Inhibitor of Metalloproteinase-1 Expression and Decreases Invasiveness of Breast Cancer Am. J. Pathol., August 1, 2006; 169(2): 633 - 642. [Abstract] [Full Text] [PDF] E. Campo Holes in SOCS in primary mediastinal large B-cell lymphoma Blood, March 15, 2005; 105(6): 2244 - 2245. [Full Text] [PDF]

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