Tissue inhibitor of metalloproteinases 1 is an autocrine and paracrine survival factor, with additional immune-regulatory functions, expressed by Hodgkin/Reed-Sternberg cells.

Abstract:

:Tissue inhibitor of metalloproteinases (TIMP)-1 and TIMP-2 are proteins with proteinase-inhibiting and cytokine properties. TIMP-1 is active primarily in B cells and B-cell lymphomas, whereas TIMP-2 expression is restricted to T cells. The expression of TIMP-1 and TIMP-2 in lymph nodes from patients with Hodgkin disease (HD) and in Hodgkin-derived cell lines was investigated. In situ hybridization showed TIMP-1 RNA expression in 3% to 80% of Hodgkin/Reed-Sternberg (H/R-S) cells from 14 of 15 patients, with results in one patient being at the lowest detection limit; no expression of TIMP-2 in H/R-S cells; and only weak expression of TIMP-2 in reactive lymphoid tissue. Production of TIMP-1 protein by H/R-S cells was accordingly found on immunohistochemical analysis of lymph nodes from patients with HD. There was only low expression of matrix metalloproteinase (MMP)-2, which is mainly inhibited by TIMP-2; no expression of MMP-1 and MMP-3 in reactive lymphoid tissue; and no expression of these MMPs in H/R-S cells. Thus, TIMP-1 expression in lymph nodes was not correlated with metalloproteinase expression. Five of 7 Hodgkin-derived cell lines expressed TIMP-1 at the protein level. Only one of these cell lines expressed TIMP-2, at the lowest detection limit. TIMP-1 levels in plasma from patients with HD were within the same range as those in plasma from healthy controls. Recombinant human TIMP-1 inhibited induced cell death in Hodgkin-derived cell lines in vitro. TIMP-1 and TIMP-2 inhibited T-cell cytotoxicity against autologous cells presenting tumor-associated antigens and in allogeneic mixed lymphocyte cultures. Thus, TIMP-1, aside from its role in proteinase equilibrium, is an autocrine and paracrine survival factor for H/R-S cells and an immunosuppressive protein expressed in Hodgkin lymphomas.

journal_name

Blood

journal_title

Blood

authors

Oelmann E,Herbst H,Zühlsdorf M,Albrecht O,Nolte A,Schmitmann C,Manzke O,Diehl V,Stein H,Berdel WE

doi

10.1182/blood.v99.1.258

subject

Has Abstract

pub_date

2002-01-01 00:00:00

pages

258-67

issue

1

eissn

0006-4971

issn

1528-0020

journal_volume

99

pub_type

杂志文章

相关文献

BLOOD文献大全
  • Survival with bone marrow transplantation versus hydroxyurea or interferon for chronic myelogenous leukemia. The German CML Study Group.

    abstract::Hydroxyurea, interferon, and HLA-identical sibling bone marrow transplantation are common therapies for chronic myelogenous leukemia (CML) in chronic phase. Which is best is controversial. The purpose of this study was to compare survival of patients with CML receiving HLA-identical sibling transplants versus hydroxyu...

    journal_title:Blood

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:

    authors: Gale RP,Hehlmann R,Zhang MJ,Hasford J,Goldman JM,Heimpel H,Hochhaus A,Klein JP,Kolb HJ,McGlave PB,Passweg JR,Rowlings PA,Sobocinski KA,Horowitz MM

    更新日期:1998-03-01 00:00:00

  • Allogeneic hematopoietic stem cell transplantation for sickle cell disease: the time is now.

    abstract::Although sickle cell disease (SCD) has a variable clinical course, many patients develop end-organ complications that are associated with significant morbidity and early mortality. Myeloablative allogeneic HSCT (allo-HSCT) is curative but has been historically performed only in children younger than 16 years of age. M...

    journal_title:Blood

    pub_type: 杂志文章,评审

    doi:10.1182/blood-2011-01-332510

    authors: Hsieh MM,Fitzhugh CD,Tisdale JF

    更新日期:2011-08-04 00:00:00

  • Vitamin D receptor-mediated skewed differentiation of macrophages initiates myelofibrosis and subsequent osteosclerosis.

    abstract::Myelofibrosis in myeloproliferative neoplasms (MPNs) with mutations such as JAK2V617F is an unfavorable sign for uncontrollable disease progression in the clinic and is complicated with osteosclerosis whose pathogenesis is largely unknown. Because several studies have revealed that macrophages are an indispensable sup...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2018-09-876615

    authors: Wakahashi K,Minagawa K,Kawano Y,Kawano H,Suzuki T,Ishii S,Sada A,Asada N,Sato M,Kato S,Shide K,Shimoda K,Matsui T,Katayama Y

    更新日期:2019-04-11 00:00:00

  • p55 and p75 tumor necrosis factor receptors in patients with chronic lymphocytic leukemia.

    abstract::We studied the expression of the two tumor necrosis factor (TNF) receptors, p55 and p75, on B cells from patients with chronic lymphocytic leukemia (CLL), and the presence of soluble TNF receptors in serum. Expression of membrane-associated receptors was quantified by double labeling of peripheral blood mononuclear ce...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Waage A,Liabakk N,Lien E,Lamvik J,Espevik T

    更新日期:1992-11-15 00:00:00

  • Concomitant inhibition of Mdm2-p53 interaction and Aurora kinases activates the p53-dependent postmitotic checkpoints and synergistically induces p53-mediated mitochondrial apoptosis along with reduced endoreduplication in acute myelogenous leukemia.

    abstract::Aberrant expression of Aurora kinases and inactivation of wild-type p53 by Mdm2 overexpression are frequent molecular events in acute myelogenous leukemia (AML), and preclinical data for inhibition of Aurora kinases or Mdm2 are promising. However, it remains largely unknown whether the viability of cells exposed to Au...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2008-01-128611

    authors: Kojima K,Konopleva M,Tsao T,Nakakuma H,Andreeff M

    更新日期:2008-10-01 00:00:00

  • Re-establishment of VWF-dependent Weibel-Palade bodies in VWD endothelial cells.

    abstract::Type 3 von Willebrand disease (VWD) is a severe hemorrhagic defect in humans. We now identify the homozygous mutation in the Chapel Hill strain of canine type 3 VWD that results in premature termination of von Willebrand factor (VWF) protein synthesis. We cultured endothelium from VWD and normal dogs to study intracel...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2004-02-0464

    authors: Haberichter SL,Merricks EP,Fahs SA,Christopherson PA,Nichols TC,Montgomery RR

    更新日期:2005-01-01 00:00:00

  • Prognostic discrimination among younger patients with chronic granulocytic leukemia: relevance to bone marrow transplantation.

    abstract::To obtain information relevant to the question of bone marrow transplantation, we examined the prognostic significance of disease features recorded at the time of diagnosis among 625 patients, aged 5 to 45, with Philadelphia chromosome-positive, nonblastic chronic granulocytic leukemia. The actuarial death rate for th...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Sokal JE,Baccarani M,Tura S,Fiacchini M,Cervantes F,Rozman C,Gomez GA,Galton DA,Canellos GP,Braun TJ

    更新日期:1985-12-01 00:00:00

  • The chronic myeloid leukemia stem cell: stemming the tide of persistence.

    abstract::Chronic myeloid leukemia (CML) is caused by the acquisition of the tyrosine kinase BCR-ABL1 in a hemopoietic stem cell, transforming it into a leukemic stem cell (LSC) that self-renews, proliferates, and differentiates to give rise to a myeloproliferative disease. Although tyrosine kinase inhibitors (TKIs) that target...

    journal_title:Blood

    pub_type: 杂志文章,评审

    doi:10.1182/blood-2016-09-696013

    authors: Holyoake TL,Vetrie D

    更新日期:2017-03-23 00:00:00

  • Hematologic effects of stem cell factor in vivo and in vitro in rodents.

    abstract::Recombinant rat stem cell factor (rrSCF) administered to rats as a single intravenous injection causes a dose-dependent neutrophilia and lymphocytosis as well as the appearance of immature myeloid cells and occasional blast cells in the circulation. Neutrophilia begins at 2 hours, peaks at 4 to 6 hours, and subsides b...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Ulich TR,del Castillo J,Yi ES,Yin S,McNiece I,Yung YP,Zsebo KM

    更新日期:1991-08-01 00:00:00

  • Reproducible obtaining of human myeloma cell lines as a model for tumor stem cell study in human multiple myeloma.

    abstract::We report a novel, reproducible methodology which enabled 10 human myeloma cell lines (HMCL) to be obtained from each of 10 tumor samples harvested from 9 patients with extramedullary proliferation. Fresh samples were cultured with interleukin 6 (IL-6) and granulocyte macrophage-colony stimulating factor (GM-CSF) at a...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Zhang XG,Gaillard JP,Robillard N,Lu ZY,Gu ZJ,Jourdan M,Boiron JM,Bataille R,Klein B

    更新日期:1994-06-15 00:00:00

  • Thrombopoietin upregulates the promoter conformation of p53 in a proliferation-independent manner coincident with a decreased expression of Bax: potential mechanisms for survival enhancing effects.

    abstract::Thrombopoietin (Tpo) has proliferative and maturational effects on immature and more committed cells, respectively. We previously reported a role for Tpo as a survival factor in the factor-dependent human cell line M07e by demonstrating that Tpo suppresses apoptosis in the absence of induced proliferation. Wild-type p...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Ritchie A,Gotoh A,Gaddy J,Braun SE,Broxmeyer HE

    更新日期:1997-12-01 00:00:00

  • Novel collectin/C1q receptor mediates mast cell activation and innate immunity.

    abstract::Mast cells play a critical role in innate immunity, allergy, and autoimmune diseases. The receptor/ligand interactions that mediate mast cell activation are poorly defined. The alpha2beta1 integrin, a receptor for collagens, laminins, decorin, E-cadherin, matrix metalloproteinase-1 (MMP-1), endorepellin, and several v...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2005-06-2218

    authors: Edelson BT,Stricker TP,Li Z,Dickeson SK,Shepherd VL,Santoro SA,Zutter MM

    更新日期:2006-01-01 00:00:00

  • Prognostic importance of structural chromosomal abnormalities in children with hyperdiploid (greater than 50 chromosomes) acute lymphoblastic leukemia.

    abstract::Approximately one fourth of children with newly diagnosed acute lymphoblastic leukemia (ALL) have hyperdiploid (greater than 50 chromosomes) blasts and a relatively favorable prognosis. Nonetheless, a substantial proportion of these patients fail therapy. We studied 138 children (70 male, 68 female) with hyperdiploid ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Pui CH,Raimondi SC,Dodge RK,Rivera GK,Fuchs LA,Abromowitch M,Look AT,Furman WL,Crist WM,Williams DL

    更新日期:1989-05-15 00:00:00

  • Antimyeloperoxidase antibodies rapidly induce alpha-4-integrin-dependent glomerular neutrophil adhesion.

    abstract::Patients with antineutrophil cytoplasmic antibodies (ANCAs) frequently develop severe vasculitis and glomerulonephritis. Although ANCAs, particularly antimyeloperoxidase (anti-MPO), have been shown to promote leukocyte adhesion in postcapillary venules, their ability to promote adhesion in the glomerular vasculature i...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2008-12-192617

    authors: Kuligowski MP,Kwan RY,Lo C,Wong C,James WG,Bourges D,Ooi JD,Abeynaike LD,Hall P,Kitching AR,Hickey MJ

    更新日期:2009-06-18 00:00:00

  • Arachidonic acid mediates interferon-gamma-induced sphingomyelin hydrolysis and monocytic marker expression in HL-60 cell line.

    abstract::The biochemical signaling mechanisms involved in transducing the effects of interferon-gamma (IFN-gamma) on human leukemia-derived HL-60 cell differentiation are not completely understood. Recent studies established the existence of a sphingomyelin (SM) cycle that operates in response to the action of IFN-gamma on HL-...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Visnjić D,Batinić D,Banfić H

    更新日期:1997-01-01 00:00:00

  • Fas antigen expression on CD34+ human marrow cells is induced by interferon gamma and tumor necrosis factor alpha and potentiates cytokine-mediated hematopoietic suppression in vitro.

    abstract::Activation of Fas antigen, a cell surface receptor molecule, by its ligand results in transduction of a signal for cell death. The Fas system has been implicated in target cell recognition, clonal development of immune effector cells, and termination of the cellular immune response. Fas antigen expression on lymphocyt...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Maciejewski J,Selleri C,Anderson S,Young NS

    更新日期:1995-06-01 00:00:00

  • Glycol-split nonanticoagulant heparins are inhibitors of hepcidin expression in vitro and in vivo.

    abstract::Hepcidin controls systemic iron availability, and its excess contributes to the anemia of chronic diseases, the most prevalent anemia in hospitalized patients. We previously reported that heparins are efficient hepcidin inhibitors both in vitro and in vivo, but their anticoagulant activity limits therapeutic use. We s...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2013-07-515221

    authors: Poli M,Asperti M,Naggi A,Campostrini N,Girelli D,Corbella M,Benzi M,Besson-Fournier C,Coppin H,Maccarinelli F,Finazzi D,Arosio P

    更新日期:2014-03-06 00:00:00

  • A monoclonal antibody (LYP18) directed against the blood platelet glycoprotein IIb/IIIa complex inhibits human melanoma growth in vivo.

    abstract::A monoclonal antibody (MoAb) (LYP18), generated against human platelet glycoprotein IIb/IIIa (GPIIb/IIIa), immuno-precipitated a IIb/IIIa-like GP complex from a highly tumorigenic human melanoma cell line (M3Dau). The M3Dau melanoma cells specifically bound 125I-labeled LYP18. To study the biologic role of these IIb/I...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Boukerche H,Berthier-Vergnes O,Bailly M,Doré JF,Leung LL,McGregor JL

    更新日期:1989-08-15 00:00:00

  • Prothrombin Houston: a dysprothrombin identifiable by crossed immunoelectrofocusing and abnormal Echis carinatus venom activation.

    abstract::A 72-yr-old male with a lifelong history of easy bruisability and posttraumatic bleeding had a prolonged prothrombin time and activated partial thromboplastin time. His plasma Stypven, Taipan, and Echis carinatus venom clotting times were prolonged. The presence of a dysprothrombin was confirmed by the discrepancy bet...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Weinger RS,Rudy C,Moake JL,Olson JD,Cimo PL

    更新日期:1980-05-01 00:00:00

  • Human herpesvirus-6 in human lymphomas: identification of specific sequences in Hodgkin's lymphomas by polymerase chain reaction.

    abstract::In search of a possible involvement of the human herpesvirus type 6 (HHV-6) in human Hodgkin's and non-Hodgkin's lymphomas, we studied the levels of anti-HHV-6 antibodies in the sera of 94 cases by an immunofluorescence assay, as well as the presence of HHV-6 sequences in the affected tissues of 66 cases by polymerase...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Torelli G,Marasca R,Luppi M,Selleri L,Ferrari S,Narni F,Mariano MT,Federico M,Ceccherini-Nelli L,Bendinelli M

    更新日期:1991-05-15 00:00:00

  • Farnesyltransferase inhibitor R115777 in myelodysplastic syndrome: clinical and biologic activities in the phase 1 setting.

    abstract::R115777 is a potent farnesyltransferase (FTase) inhibitor with substantial antitumor activity in preclinical models. We conducted a phase 1 study (3 + 3 design) of R115777 in patients with myelodysplastic syndrome (MDS). R115777 was administered twice daily (3-weeks-on/1-week-off schedule for 8 weeks) (starting dosage...

    journal_title:Blood

    pub_type: 临床试验,杂志文章

    doi:10.1182/blood-2002-11-3359

    authors: Kurzrock R,Kantarjian HM,Cortes JE,Singhania N,Thomas DA,Wilson EF,Wright JJ,Freireich EJ,Talpaz M,Sebti SM

    更新日期:2003-12-15 00:00:00

  • Erythropoiesis-stimulating factor production by rabbit kidney cultures from "programmed" rabbits.

    abstract::Rabbit kidney tissue either from normal rabbits or from rabbits "programmed" by phlebotomy or varying periods of hypoxia was cultured and shown to release into the culture medium an erythropoietically active substance. The cultures established from rabbits programmed by 6-12 hr of hypoxia yielded the highest levels of...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Ogle JW,Lange RD,Dunn CD

    更新日期:1978-07-01 00:00:00

  • Detection of Epstein-Barr virus messenger RNA in Reed-Sternberg cells of Hodgkin's disease by in situ hybridization with biotinylated probes on specially processed modified acetone methyl benzoate xylene (ModAMeX) sections.

    abstract::Microscopic intracellular detection of Epstein-Barr virus (EBV) messenger RNA in Reed-Sternberg cells of Hodgkin's disease (HD) was possible by in situ hybridization, in tissue sections prepared by a method termed modified acetone methyl benzoate xylene (ModAMeX). The ModAMeX method was initially developed for simulta...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Brousset P,Chittal S,Schlaifer D,Icart J,Payen C,Rigal-Huguet F,Voigt JJ,Delsol G

    更新日期:1991-04-15 00:00:00

  • Reticulocyte-secreted exosomes bind natural IgM antibodies: involvement of a ROS-activatable endosomal phospholipase iPLA2.

    abstract::Reticulocytes release small membrane vesicles termed exosomes during their maturation into erythrocytes. It has been suggested that reticulocytes remodel the plasma membrane of the immature red cell during erythropoiesis by specifically eliminating various proteins. We report here that exosome release is associated wi...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2007-04-085845

    authors: Blanc L,Barres C,Bette-Bobillo P,Vidal M

    更新日期:2007-11-01 00:00:00

  • A novel regulator of G-protein signaling bearing GAP activity for Galphai and Galphaq in megakaryocytes.

    abstract::The regulator of G-protein signaling (RGS) negatively regulates the alpha subunit of G proteins by accelerating their intrinsic guanosine triphosphatase (GTPase) activity. Here are reported the isolation and characterization of a novel mouse RGS, termed RGS18, which is a new member of RGS subfamily B. Northern blot an...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood.v97.10.3051

    authors: Nagata Y,Oda M,Nakata H,Shozaki Y,Kozasa T,Todokoro K

    更新日期:2001-05-15 00:00:00

  • Expression and release of CD27 in human B-cell malignancies.

    abstract::CD27, a transmembrane disulfide-linked 55-kD homodimer, belongs to the nerve growth factor-receptor family, a group of homologous molecules involved in lymphocyte differentiation and selection. It is expressed on mature thymocytes, peripheral blood T cells, and a subpopulation of B cells. We investigated the expressio...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: van Oers MH,Pals ST,Evers LM,van der Schoot CE,Koopman G,Bonfrer JM,Hintzen RQ,von dem Borne AE,van Lier RA

    更新日期:1993-12-01 00:00:00

  • The t(15;17) breakpoint in acute promyelocytic leukemia cluster within two different sites of the myl gene: targets for the detection of minimal residual disease by the polymerase chain reaction.

    abstract::The retinoic acid receptor alpha (RAR alpha) and the myl gene are involved in the translocation breakpoint t(15;17)(q22;q21) in acute promyelocytic leukemia (APL). The majority of the breakpoint sites have been mapped within the second intron of the RAR alpha gene; however, the breakpoint sites on the myl gene are var...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Chang KS,Lu JF,Wang G,Trujillo JM,Estey E,Cork A,Chu DT,Freireich EJ,Stass SA

    更新日期:1992-02-01 00:00:00

  • Next-generation sequencing of the TET2 gene in 355 MDS and CMML patients reveals low-abundance mutant clones with early origins, but indicates no definite prognostic value.

    abstract::Mutations in the TET2 gene are frequent in myeloid disease, although their biologic and prognostic significance remains unclear. We analyzed 355 patients with myelodysplastic syndromes using "next-generation" sequencing for TET2 aberrations, 91 of whom were also subjected to single-nucleotide polymorphism 6.0 array ka...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2010-03-274704

    authors: Smith AE,Mohamedali AM,Kulasekararaj A,Lim Z,Gäken J,Lea NC,Przychodzen B,Mian SA,Nasser EE,Shooter C,Westwood NB,Strupp C,Gattermann N,Maciejewski JP,Germing U,Mufti GJ

    更新日期:2010-11-11 00:00:00

  • Granulated T cell lymphocytosis with neutropenia: malignant or benign chronic lymphoproliferative disorder?

    abstract::The clinical, morphological, immunologic, and cytogenetic features of seven cases of chronic granulated T cell lymphocytosis with neutropenia were studied. The disorder was characterized by moderate blood and bone marrow lymphocytosis, neutropenia, polyclonal hypergammaglobulinemia, splenomegaly, absence of lymphadeno...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: McKenna RW,Arthur DC,Gajl-Peczalska KJ,Flynn P,Brunning RD

    更新日期:1985-08-01 00:00:00

  • Isolation of Reed-Sternberg cells from lymph nodes of Hodgkin's disease patients.

    abstract::This study describes a simple and relatively rapid method of purifying Reed-Sternberg (R-S) cells and their morphologic variants from the lymph nodes of patients affected by Hodgkin's disease. Our initial studies defined the optimal procedure for a quantitative disaggregation of Hodgkin's lymph nodes and the densities...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Sitar G,Brusamolino E,Bernasconi C,Ascari E

    更新日期:1989-01-01 00:00:00