Tissue inhibitor of metalloproteinase (TIMP)-1 induces differentiation and an antiapoptotic phenotype in germinal center B cells.
Tissue inhibitors of metalloproteinases (TIMPs) have been shown to be multifunctional factors. Contrasting with their enzyme-inhibitory activity, TIMPs also promote cell growth. Previously, we have reported an enhanced expression of TIMP-1 by normal reactive B cells and high-grade lymphomas. In the present study, a series of Burkitt's lymphoma (BL) cell lines were analyzed for their expression of TIMP-1. TIMP-1 expression correlates with upregulation of activation and survival markers. TIMP-1-negative cells express the phenotype associated with group I BL lines and Epstein-Barr virus (EBV)-negative, nonendemic BLs (CD10+, CD38+, sIg+, and CD77+). However, TIMP-1+ BL lines showed group II/III BL phenotype, downregulation of the above markers, and upregulation and secretion of the activation marker CD23. Also, TIMP-1+ cells have high levels of CD40 expression. To determine whether TIMP-1 is directly involved in the BL phenotype, an EBV-negative BL line JD38 was infected with timp-1-expressing retrovirus and analyzed. In the absence of EBV, upregulation of TIMP-1 is sufficient to induce the same phenotype seen in TIMP-1+, EBV+ BL lines (CD10-, CD38-, sIg-, CD77-, CD23+, CD40 bright). This study not only suggests a role for TIMP-1 in BLs, but also supports its value as a prognostic factor. This is a US government work. There are no restrictions on its use.
Hematopathology Section, Laboratory of Pathology, National Cancer Institute, Bethesda, MD 20892, USA.
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Guedez
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Courtemanch
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Stetler-Stevenson
D017209:Apoptosis / Q000187:drug effects; D016175:B-Lymphocyte Subsets / Q000187:drug effects* / Q000473:pathology; D002051:Burkitt Lymphoma / Q000378:metabolism / Q000473:pathology / Q000821:virology; D002454:Cell Differentiation / Q000187:drug effects; D054278:Embryonal Carcinoma Stem Cells; D018858:Germinal Center / Q000473:pathology*; D006566:Herpesviridae Infections / Q000378:metabolism / Q000473:pathology; D004854:Herpesvirus 4, Human; D006801:Humans; D007075:Immunoglobulin M / Q000032:analysis; D009363:Neoplasm Proteins / Q000502:physiology; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000473:pathology; D015260:Neprilysin / Q000032:analysis; D010641:Phenotype; D017455:Receptors, IgE / Q000032:analysis; D011993:Recombinant Fusion Proteins / Q000502:physiology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000502:physiology*; D014162:Transfection; D014281:Trihexosylceramides / Q000032:analysis; D014407:Tumor Cells, Cultured; D014412:Tumor Virus Infections / Q000378:metabolism / Q000473:pathology
D007075:Immunoglobulin M; D009363:Neoplasm Proteins; D017455:Receptors, IgE; D011993:Recombinant Fusion Proteins; D019715:Tissue Inhibitor of Metalloproteinase-1; D014281:Trihexosylceramides; C018549:globotriaosylceramide; D015260:Neprilysin