Myeloma cells upregulate interleukin-6 secretion in osteoblastic cells through cell-to-cell contact but downregulate osteocalcin.

Abstract:

:Previous studies have shown that bone marrow, especially the bone microenvironment, may play an important role in the pathogenesis of multiple myeloma (MM). To elucidate the relationship between myeloma cells and bone cells, mainly osteoblasts, we have established a coculture system between two interleukin-6 (IL-6)-dependent myeloma cell lines, XG1 and XG6, and the osteosarcoma cell lines Saos-2 and MG63. Both osteosarcoma cell lines have retained major functions of normal osteoblasts; principally, the capacity to produce hematopoietic growth factors (including IL-6) and osteocalcin, a noncollagenic protein essential in the bone formation process. Because IL-6 is a critical growth factor in MM, we have examined the IL-6 osteoblastic cell production in our coculture system. XG1 cells strongly upregulate IL-6 production by MG63 and Saos-2 cells. Of major interest, the triggering of IL-6 is totally dependent on the physical contact between myeloma cells and osteoblastic cells, contact that is partly mediated by CD44, CD56, and fibronectin interactions. Osteocalcin production by MG63 and Saos-2 cells has previously been shown to be dependent on 1,25-(OH)2D3. We demonstrate that XG1 and XG6 cells reduced the amount of osteocalcin in MG63 coculture cell supernatants, a reduction that is partly mediated by a soluble factor and by cell-to-cell contact. Notably, whereas one of the myeloma cell lines, XG6, has lost its capacity to stimulate IL-6 production by osteoblastic cell lines, both XG1 and XG6 cell lines remain able to reduce the osteocalcin amount, indicating that IL-6 and osteocalcin levels are regulated by two different pathways. In conclusion, these data strongly support the concept that the bone microenvironment is directly modified by contact with myeloma cells and are consistent with the characteristics observed in vivo in patients with MM patients, ie, abnormally high IL-6 and low osteocalcin levels, respectively.

journal_name

Blood

journal_title

Blood

authors

Barillé S,Collette M,Bataille R,Amiot M

subject

Has Abstract

pub_date

1995-10-15 00:00:00

pages

3151-9

issue

8

eissn

0006-4971

issn

1528-0020

journal_volume

86

pub_type

杂志文章

相关文献

BLOOD文献大全
  • Platelet-TLR7 mediates host survival and platelet count during viral infection in the absence of platelet-dependent thrombosis.

    abstract::Viral infections have been associated with reduced platelet counts, the biological significance of which has remained elusive. Here, we show that infection with encephalomyocarditis virus (EMCV) rapidly reduces platelet count, and this response is attributed to platelet Toll-like receptor 7 (TLR7). Platelet-TLR7 stimu...

    journal_title:Blood

    pub_type: 临床试验,杂志文章

    doi:10.1182/blood-2013-11-536003

    authors: Koupenova M,Vitseva O,MacKay CR,Beaulieu LM,Benjamin EJ,Mick E,Kurt-Jones EA,Ravid K,Freedman JE

    更新日期:2014-07-31 00:00:00

  • Regulation of ITAM-positive receptors: role of IL-12 and IL-18.

    abstract::Our previous studies have identified mechanisms by which cytokine production, blocked by Ly49G2 receptor cross-linking, can be overridden. In this study we analyzed the regulation of other ITAM-positive receptor signaling on NK, NKT, and T cells and characterized the biochemical pathways involved in this signaling. Ou...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2005-04-1579

    authors: Ortaldo JR,Winkler-Pickett R,Wigginton J,Horner M,Bere EW,Mason AT,Bhat N,Cherry J,Sanford M,Hodge DL,Young HA

    更新日期:2006-02-15 00:00:00

  • Inhibition of in vitro angiogenesis by platelet factor-4-derived peptides and mechanism of action.

    abstract::In this study, we examined in detail the interaction of platelet factor-4 (PF-4) with fibroblast growth factor-2 (FGF-2) and vascular endothelial growth factor (VEGF) and the effect of PF-4-derived synthetic peptides. We show that a peptide between amino acids 47 and 70 that contains the heparin-binding lysine-rich si...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Jouan V,Canron X,Alemany M,Caen JP,Quentin G,Plouet J,Bikfalvi A

    更新日期:1999-08-01 00:00:00

  • Stage-dependent effect of deferoxamine on growth of Plasmodium falciparum in vitro.

    abstract::Deferoxamine (DF) has antimalarial activity that can be demonstrated in vitro and in vivo. This study is designed to examine the speed of onset and stage dependency of growth inhibition by DF and to determine whether its antimalarial activity is cytostatic or cytocidal. Growth inhibition was assessed by suppression of...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Whitehead S,Peto TE

    更新日期:1990-09-15 00:00:00

  • FLT3/FLK2 ligand promotes the growth of murine stem cells and the expansion of colony-forming cells and spleen colony-forming units.

    abstract::The effect of FLT3/FLK2 ligand (FL) on the growth of primitive hematopoietic cells was investigated using ThyloSca1+ stem cells. FL was observed to interact with a variety of factors to initiate colony formation by stem cells. When stem cells were stimulated in liquid culture with FL plus interleukin (IL)-3, IL-6, gra...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Hudak S,Hunte B,Culpepper J,Menon S,Hannum C,Thompson-Snipes L,Rennick D

    更新日期:1995-05-15 00:00:00

  • Dasatinib crosses the blood-brain barrier and is an efficient therapy for central nervous system Philadelphia chromosome-positive leukemia.

    abstract::Although imatinib, a BCR-ABL tyrosine kinase inhibitor, is used to treat acute Philadelphia chromosome-positive (Ph(+)) leukemia, it does not prevent central nervous system (CNS) relapses resulting from poor drug penetration through the blood-brain barrier. Imatinib and dasa-tinib (a dual-specific SRC/BCR-ABL kinase i...

    journal_title:Blood

    pub_type: 临床试验,杂志文章

    doi:10.1182/blood-2008-02-140665

    authors: Porkka K,Koskenvesa P,Lundán T,Rimpiläinen J,Mustjoki S,Smykla R,Wild R,Luo R,Arnan M,Brethon B,Eccersley L,Hjorth-Hansen H,Höglund M,Klamova H,Knutsen H,Parikh S,Raffoux E,Gruber F,Brito-Babapulle F,Dombret H,Dua

    更新日期:2008-08-15 00:00:00

  • Beyond hairy cell: the activity of cladribine in other hematologic malignancies.

    abstract::Before the contemporary development of rationally designed antineoplastic therapies, cladribine was identified as a lymphocyte-specific agent. Its profound impact on the natural history of hairy cell leukemia, with responses approaching 100% and a median duration of response of nearly a decade after only a single 7-da...

    journal_title:Blood

    pub_type: 杂志文章,评审

    doi:10.1182/blood-2010-02-246140

    authors: Sigal DS,Miller HJ,Schram ED,Saven A

    更新日期:2010-10-21 00:00:00

  • Management and clinical outcomes in patients treated with apixaban vs warfarin undergoing procedures.

    abstract::Using data from ARISTOTLE, we describe the periprocedural management of anticoagulation and rates of subsequent clinical outcomes among patients chronically anticoagulated with warfarin or apixaban. We recorded whether (and for how long) anticoagulant therapy was interrupted preprocedure, whether bridging therapy was ...

    journal_title:Blood

    pub_type: 杂志文章,多中心研究,随机对照试验

    doi:10.1182/blood-2014-08-595496

    authors: Garcia D,Alexander JH,Wallentin L,Wojdyla DM,Thomas L,Hanna M,Al-Khatib SM,Dorian P,Ansell J,Commerford P,Flaker G,Lanas F,Vinereanu D,Xavier D,Hylek EM,Held C,Verheugt FW,Granger CB,Lopes RD

    更新日期:2014-12-11 00:00:00

  • Toward a stem cell gene therapy for breast cancer.

    abstract::Current approaches for treatment of late-stage breast cancer rarely result in a long-term cure. In part this is due to tumor stroma that prevents access of systemically or intratumorally applied therapeutics. We propose a stem cell gene therapy approach for controlled tumor stroma degradation that uses the pathophysio...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2008-10-187237

    authors: Li Z,Liu Y,Tuve S,Xun Y,Fan X,Min L,Feng Q,Kiviat N,Kiem HP,Disis ML,Lieber A

    更新日期:2009-05-28 00:00:00

  • T-cell defect in diffuse large B-cell lymphomas involves expansion of myeloid-derived suppressor cells.

    abstract::In diffuse large B-cell lymphoma (DLBCL), the number of circulating monocytes and neutrophils represents an independent prognostic factor. These cell subsets include monocytic and granulocytic myeloid-derived suppressor cells (M- and G-MDSCs) defined by their ability to suppress T-cell responses. MDSCs are a heterogen...

    journal_title:Blood

    pub_type: 临床试验,杂志文章

    doi:10.1182/blood-2015-08-662783

    authors: Azzaoui I,Uhel F,Rossille D,Pangault C,Dulong J,Le Priol J,Lamy T,Houot R,Le Gouill S,Cartron G,Godmer P,Bouabdallah K,Milpied N,Damaj G,Tarte K,Fest T,Roussel M

    更新日期:2016-08-25 00:00:00

  • ICA-17043, a novel Gardos channel blocker, prevents sickled red blood cell dehydration in vitro and in vivo in SAD mice.

    abstract::A prominent feature of sickle cell anemia is the presence of dehydrated red blood cells (RBCs) in circulation. Loss of potassium (K(+)), chloride (Cl(-)), and water from RBCs is thought to contribute to the production of these dehydrated cells. One main route of K(+) loss in the RBC is the Gardos channel, a calcium (C...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2002-05-1433

    authors: Stocker JW,De Franceschi L,McNaughton-Smith GA,Corrocher R,Beuzard Y,Brugnara C

    更新日期:2003-03-15 00:00:00

  • Spectrum of clinical presentations in familial hemophagocytic lymphohistiocytosis type 5 patients with mutations in STXBP2.

    abstract::Hemophagocytic lymphohistiocytosis (HLH) is an often-fatal hyperinflammatory syndrome characterized by fever, hepatosplenomegaly, cytopenia, and in some cases hemophagocytosis. Here, we describe the mutation analysis, clinical presentation, and functional analysis of natural killer (NK) cells in patients with mutation...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2010-05-282541

    authors: Meeths M,Entesarian M,Al-Herz W,Chiang SC,Wood SM,Al-Ateeqi W,Almazan F,Boelens JJ,Hasle H,Ifversen M,Lund B,van den Berg JM,Gustafsson B,Hjelmqvist H,Nordenskjöld M,Bryceson YT,Henter JI

    更新日期:2010-10-14 00:00:00

  • Prolonged expression of c-fos suppresses cell cycle entry of dormant hematopoietic stem cells.

    abstract::The proto-oncogene c-fos was transiently upregulated in primitive hematopoietic stem (Lin-Sca-1(+)) cells stimulated with stem cell factor, interleukin-3 (IL-3), and IL-6. To investigate a role of the c-fos in hematopoietic stem cells, we used bone marrow (BM) cells from transgenic mice carrying the c-fos gene under t...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Okada S,Fukuda T,Inada K,Tokuhisa T

    更新日期:1999-02-01 00:00:00

  • The CD28 family: a T-cell rheostat for therapeutic control of T-cell activation.

    abstract::The CD28 family of receptors (CD28, cytotoxic T-lymphocyte-associated antigen 4 [CTLA-4], inducible costimulator [ICOS], program death-1 [PD-1], and B- and T-lymphocyte attenuator [BTLA]) plays a critical role in controlling the adaptive arm of the immune response. While considerable information is available regarding...

    journal_title:Blood

    pub_type: 杂志文章,评审

    doi:10.1182/blood-2004-04-1596

    authors: Riley JL,June CH

    更新日期:2005-01-01 00:00:00

  • Platelet αIIbβ3 activation: filling in the pieces.

    abstract::In this issue of Blood, Kasirer-Friede and colleagues show that the adhesion and degranulation promoter protein (ADAP) promotes αIIbβ3 activation by presenting the cytoplasmic proteins talin and kindlin to the β3 cytoplasmic tail. ...

    journal_title:Blood

    pub_type: 评论,杂志文章

    doi:10.1182/blood-2014-02-557355

    authors: Bennett JS

    更新日期:2014-05-15 00:00:00

  • Targeting BCL-2 in B-cell lymphomas.

    abstract::The B-cell leukemia/lymphoma-2 (BCL-2) family of proteins governs the intrinsic pathway of mitochondrial apoptosis. Dysregulation of BCL-2 has long been known to be a crucial part of the pathophysiology of B-cell lymphomas; however, several early attempts to target this pathway therapeutically were unsuccessful becaus...

    journal_title:Blood

    pub_type: 杂志文章,评审

    doi:10.1182/blood-2017-04-737338

    authors: Davids MS

    更新日期:2017-08-31 00:00:00

  • Corepressor Rcor1 is essential for murine erythropoiesis.

    abstract::The corepressor Rcor1 has been linked biochemically to hematopoiesis, but its function in vivo remains unknown. We show that mice deleted for Rcor1 are profoundly anemic and die in late gestation. Definitive erythroid cells from mutant mice arrest at the transition from proerythroblast to basophilic erythroblast. Rema...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2013-11-538678

    authors: Yao H,Goldman DC,Nechiporuk T,Kawane S,McWeeney SK,Tyner JW,Fan G,Kerenyi MA,Orkin SH,Fleming WH,Mandel G

    更新日期:2014-05-15 00:00:00

  • The kringle stabilizes urokinase binding to the urokinase receptor.

    abstract::The structural basis of the interaction between single-chain urokinase-type plasminogen activator (scuPA) and its receptor (uPAR) is incompletely defined. Several observations indicated the kringle facilitates the binding of uPA to uPAR. A scuPA variant lacking the kringle (Delta K-scuPA) bound to soluble uPAR (suPAR)...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2003-03-0949

    authors: Bdeir K,Kuo A,Sachais BS,Rux AH,Bdeir Y,Mazar A,Higazi AA,Cines DB

    更新日期:2003-11-15 00:00:00

  • Mutually exclusive recurrent somatic mutations in MAP2K1 and BRAF support a central role for ERK activation in LCH pathogenesis.

    abstract::Langerhans cell histiocytosis (LCH) is a myeloproliferative disorder characterized by lesions composed of pathological CD207(+) dendritic cells with an inflammatory infiltrate. BRAFV600E remains the only recurrent mutation reported in LCH. In order to evaluate the spectrum of somatic mutations in LCH, whole exome sequ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2014-05-577825

    authors: Chakraborty R,Hampton OA,Shen X,Simko SJ,Shih A,Abhyankar H,Lim KP,Covington KR,Trevino L,Dewal N,Muzny DM,Doddapaneni H,Hu J,Wang L,Lupo PJ,Hicks MJ,Bonilla DL,Dwyer KC,Berres ML,Poulikakos PI,Merad M,McClain K

    更新日期:2014-11-06 00:00:00

  • Blood transfusions and immunophenotypic alterations of lymphocyte subsets in sickle cell anemia. The Transfusion Safety Study Group.

    abstract::Transfusions purportedly induce dysfunction of cell-mediated immunity in sickle cell anemia (SCA). We studied hematologic and lymphocytic indices in 173 human immunodeficiency virus (HIV)-negative subjects with SCA and 131 black controls. Children aged 1 to 7 years with SCA had leukocyte counts and percentages of gran...

    journal_title:Blood

    pub_type: 杂志文章,多中心研究

    doi:

    authors: Wong WY,Powars DR,Operskalski EA,Hassett J,Parker JW,Sarnaik S,Pegelow CH,Hilgartner MW,Johnson CS,Zhou Y

    更新日期:1995-04-15 00:00:00

  • Effective induction of naive and recall T-cell responses by targeting antigen to human dendritic cells via a humanized anti-DC-SIGN antibody.

    abstract::Current dendritic cell (DC)-based vaccines are based on ex vivo-generated autologous DCs loaded with antigen prior to readministration into patients. A more direct and less laborious strategy is to target antigens to DCs in vivo via specific surface receptors. Therefore, we developed a humanized antibody, hD1V1G2/G4 (...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2005-01-0318

    authors: Tacken PJ,de Vries IJ,Gijzen K,Joosten B,Wu D,Rother RP,Faas SJ,Punt CJ,Torensma R,Adema GJ,Figdor CG

    更新日期:2005-08-15 00:00:00

  • Aspirin and salicylate induce apoptosis and activation of caspases in B-cell chronic lymphocytic leukemia cells.

    abstract::We analyzed the effect of aspirin, salicylate, and other nonsteroidal antiinflammatory drugs (NSAIDs) on the viability of B-chronic lymphocytic leukemia (B-CLL) cells. Aspirin induced a decrease in cell viability in a dose- and time-dependent manner. The mean IC50 for cells from 5 patients was 5.9 +/- 1.13 mmol/L (ran...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Bellosillo B,Piqué M,Barragán M,Castaño E,Villamor N,Colomer D,Montserrat E,Pons G,Gil J

    更新日期:1998-08-15 00:00:00

  • FERM domain mutations induce gain of function in JAK3 in adult T-cell leukemia/lymphoma.

    abstract::Adult T-cell leukemia/lymphoma (ATLL) is an incurable disease where most patients succumb within the first year of diagnosis. Both standard chemotherapy regimens and mAbs directed against ATLL tumor markers do not alter this aggressive clinical course. Therapeutic development would be facilitated by the discovery of g...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2010-12-319467

    authors: Elliott NE,Cleveland SM,Grann V,Janik J,Waldmann TA,Davé UP

    更新日期:2011-10-06 00:00:00

  • Elevated interleukin-7 levels not sufficient to maintain T-cell homeostasis during simian immunodeficiency virus-induced disease progression.

    abstract::Elevated levels of interleukin 7 (IL-7) have been correlated with various T-cell depletion conditions, including HIV infection, and suggested as an indicator of HIV disease progression (AIDS and death). Here, the assessment of pathogenic simian immunodeficiency virus (SIVmac239) infection in rhesus macaques demonstrat...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2003-03-0874

    authors: Muthukumar A,Wozniakowski A,Gauduin MC,Paiardini M,McClure HM,Johnson RP,Silvestri G,Sodora DL

    更新日期:2004-02-01 00:00:00

  • Metformin induces FOXO3-dependent fetal hemoglobin production in human primary erythroid cells.

    abstract::Induction of red blood cell (RBC) fetal hemoglobin (HbF; α2γ2) ameliorates the pathophysiology of sickle cell disease (SCD) by reducing the concentration of sickle hemoglobin (HbS; α2βS2) to inhibit its polymerization. Hydroxyurea (HU), the only US Food and Drug Administration (FDA)-approved drug for SCD, acts in part...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2017-11-814335

    authors: Zhang Y,Paikari A,Sumazin P,Ginter Summarell CC,Crosby JR,Boerwinkle E,Weiss MJ,Sheehan VA

    更新日期:2018-07-19 00:00:00

  • The sixth sense: hematopoietic stem cells detect danger through purinergic signaling.

    abstract::Over the past decade, extracellular nucleotides (such as ATP and UTP) have emerged as key immunomodulators. This family of molecules, already known for its key metabolic functions, has been the focus of intense investigation that has unambiguously shown its crucial role as mediators of cell-to-cell communication. More...

    journal_title:Blood

    pub_type: 杂志文章,评审

    doi:10.1182/blood-2012-04-422378

    authors: Rossi L,Salvestrini V,Ferrari D,Di Virgilio F,Lemoli RM

    更新日期:2012-09-20 00:00:00

  • Structural basis for quinine-dependent antibody binding to platelet integrin αIIbβ3.

    abstract::Drug-induced immune thrombocytopenia (DITP) is caused by antibodies that react with specific platelet-membrane glycoproteins when the provoking drug is present. More than 100 drugs have been implicated as triggers for this condition, quinine being one of the most common. The cause of DITP in most cases appears to be a...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2015-04-639351

    authors: Zhu J,Zhu J,Bougie DW,Aster RH,Springer TA

    更新日期:2015-10-29 00:00:00

  • Activation of the CD95 (APO-1/Fas) system in T cells from human immunodeficiency virus type-1-infected children.

    abstract::Increased apoptosis of CD4+ T cells is considered to be involved in CD4+ T-cell depletion in human immunodeficiency virus type-1 (HIV-1)-infected individuals progressing toward acquired immunodeficiency syndrome (AIDS). We have recently shown that CD95 (APO-1/Fas) expression is strongly increased in T cells of HIV-1-i...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Bäumler CB,Böhler T,Herr I,Benner A,Krammer PH,Debatin KM

    更新日期:1996-09-01 00:00:00

  • Interleukin-1, tumor necrosis factor, and the production of colony-stimulating factors by cultured mesenchymal cells.

    abstract::Although the genes for four hematopoietic colony-stimulating factors (CSFs) have been cloned, neither the mechanism of the regulation of their production nor their cellular origins have been established with certainty. Monocytes are known to produce colony-stimulating and burst-promoting activities, as well as several...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Sieff CA,Niemeyer CM,Mentzer SJ,Faller DV

    更新日期:1988-10-01 00:00:00

  • The clinical significance of NOTCH1 and SF3B1 mutations in the UK LRF CLL4 trial.

    abstract::NOTCH1 and SF3B1 mutations have been previously reported to have prognostic significance in chronic lymphocytic leukemia but to date they have not been validated in a prospective, controlled clinical trial. We have assessed the impact of these mutations in a cohort of 494 patients treated within the randomized phase 3...

    journal_title:Blood

    pub_type: 杂志文章,随机对照试验

    doi:10.1182/blood-2012-05-429282

    authors: Oscier DG,Rose-Zerilli MJ,Winkelmann N,Gonzalez de Castro D,Gomez B,Forster J,Parker H,Parker A,Gardiner A,Collins A,Else M,Cross NC,Catovsky D,Strefford JC

    更新日期:2013-01-17 00:00:00