402
Views
0
CrossRef citations to date
0
Altmetric
Review

Possible targets to treat myeloma-related osteoclastogenesis

, , , , &
Pages 325-336 | Received 10 Jan 2018, Accepted 28 Feb 2018, Published online: 09 Mar 2018

References

  • Palumbo A, Anderson K. Multiple myeloma. N Engl J Med. 2011;364:1046–1060.
  • Roodman GD. Pathogenesis of myeloma bone disease. Leukemia. 2009;23:435–441.
  • Yaccoby S. Advances in the understanding of myeloma bone disease and tumour growth. Br J Haematol. 2010;149:311–321.
  • Kyle RA, Gertz MA, Witzig TE, et al. Review of 1027 patients with newly diagnosed multiple myeloma. Mayo Clin Proc. 2003;78:21–33.
  • Silbermann R, Roodman GD. Current controversies in the management of myeloma bone disease. J Cell Physiol. 2016;231:2374–2379.
  • Terpos E, Berenson J, Raje N, et al. Management of bone disease in multiple myeloma. Expert Rev Hematol. 2014;7:113–125.
  • Terpos E, Christoulas D, Gavriatopoulou M. Biology and treatment of myeloma related bone disease. Metabolism. 2018;80:80–90.
  • Morgan GJ, Davies FE, Gregory WM, et al. Long-term follow-up of MRC Myeloma IX trial: survival outcomes with bisphosphonate and thalidomide treatment. Clin Cancer Res. 2013;19:6030–6038.
  • Frediani B, Baraldi E, Cremonesi G. Effect of clodronate treatment on risk of fracture: a systematic review and meta-analysis. Calcif Tissue Int. 2014;95:295–307.
  • Gavriatopoulou M, Dimopoulos MA, Kastritis E, et al. Emerging treatment approaches for myeloma-related bone disease. Expert Rev Hematol. 2017;10:217–228.
  • Choi SJ, Cruz JC, Craig F, et al. Macrophage inflammatory protein 1-alpha is a potential osteoclast stimulatory factor in multiple myeloma. Blood. 2000;96:671–675.
  • Lee JW, Chung HY, Ehrlich LA, et al. IL-3 expression by myeloma cells increases both osteoclast formation and growth of myeloma cells. Blood. 2004;103:2308–2315.
  • Kitaura H, Sands MS, Aya K, et al. Marrow stromal cells and osteoclast precursors differentially contribute to TNF-alpha-induced osteoclastogenesis in vivo. J Immunol. 2004;173:4838–4846.
  • Asagiri M, Takayanagi H. The molecular understanding of osteoclast differentiation. Bone. 2007;40:251–264.
  • Delgado-Calle J, Anderson J, Cregor MD, et al. Bidirectional notch signaling and osteocyte-derived factors in the bone marrow microenvironment promote tumor cell proliferation and bone destruction in multiple myeloma. Cancer Res. 2016;76:1089–1100.
  • Ehrlich LA, Chung HY, Ghobrial I, et al. IL-3 is a potential inhibitor of osteoblast differentiation in multiple myeloma. Blood. 2005;106:1407–1414.
  • Silbermann R, Bolzoni M, Storti P, et al. Bone marrow monocyte-/macrophage-derived activin A mediates the osteoclastogenic effect of IL-3 in multiple myeloma. Leukemia. 2014;28:951–954.
  • Danks L, Takayanagi H. Immunology and bone. J Biochem. 2013;154:29–39.
  • Giuliani N, Lisignoli G, Colla S, et al. CC-chemokine ligand 20/macrophage inflammatory protein-3alpha and CC-chemokine receptor 6 are overexpressed in myeloma microenvironment related to osteolytic bone lesions. Cancer Res. 2008;68:6840–6850.
  • Roodman GD. Role of the bone marrow microenvironment in multiple myeloma. J Bone Miner Res. 2002;17:1921–1925.
  • Pearse RN, Sordillo EM, Yaccoby S, et al. Multiple myeloma disrupts the TRANCE/osteoprotegerin cytokine axis to trigger bone destruction and promote tumor progression. Proc Natl Acad Sci U S A. 2001;98:11581–11586.
  • Colucci S, Brunetti G, Rizzi R, et al. T cells support osteoclastogenesis in an in vitro model derived from human multiple myeloma bone disease: the role of the OPG/TRAIL interaction. Blood. 2004;104:3722–3730.
  • Colucci S, Brunetti G, Mori G, et al. Soluble decoy receptor 3 modulates the survival and formation of osteoclasts from multiple myeloma bone disease patients. Leukemia. 2009;23:2139–2146.
  • Brunetti G, Rizzi R, Oranger A, et al. LIGHT/TNFSF14 increases osteoclastogenesis and decreases osteoblastogenesis in multiple myeloma-bone disease. Oncotarget. 2014;5:12950–12967.
  • Noonan K, Marchionni L, Anderson J, et al. A novel role of IL-17-producing lymphocytes in mediating lytic bone disease in multiple myeloma. Blood. 2010;116:3554–3563.
  • Prabhala RH, Pelluru D, Fulciniti M, et al. Elevated IL-17 produced by TH17 cells promotes myeloma cell growth and inhibits immune function in multiple myeloma. Blood. 2010;115:5385–5392.
  • Dhodapkar KM, Barbuto S, Matthews P, et al. Dendritic cells mediate the induction of polyfunctional human IL17-producing cells (Th17-1 cells) enriched in the bone marrow of patients with myeloma. Blood. 2008;112:2878–2885.
  • Lee OL, Horvath N, Lee C, et al. Bisphosphonate guidelines for treatment and prevention of myeloma bone disease. Intern Med J. 2017;47:938–951.
  • Kostenuik PJ, Nguyen HQ, McCabe J, et al. Denosumab, a fully human monoclonal antibody to RANKL, inhibits bone resorption and increases BMD in knock-in mice that express chimeric (murine/human) RANKL. J Bone Miner Res. 2009;24:182–195.
  • Vij R, Horvath N, Spencer A, et al. An open-label, phase 2 trial of denosumab in the treatment of relapsed or plateau-phase multiple myeloma. Am J Hematol. 2009;84:650–656.
  • Henry DH, Costa L, Goldwasser F, et al. Randomized, double-blind study of denosumab versus zoledronic acid in the treatment of bone metastases in patients with advanced cancer (excluding breast and prostate cancer) or multiple myeloma. J Clin Oncol. 2011;29:1125–1132.
  • Lipton A, Fizazi K, Stopeck AT, et al. Superiority of denosumab to zoledronic acid for prevention of skeletal-related events: a combined analysis of 3 pivotal, randomised, phase 3 trials. Eur J Cancer. 2012;48:3082–3092.
  • Raje N, Vadhan-Raj S, Willenbacher W, et al. Evaluating results from the multiple myeloma patient subset treated with denosumab or zoledronic acid in a randomized phase 3 trial. Blood Cancer J. 2016;6:e378.
  • Raje N, Terpos E, Willenbacher W, et al. Denosumab versus zoledronic acid in bone disease treatment of newly diagnosed multiple myeloma: an international, double-blind, double-dummy, randomised, controlled, phase 3 study. Lancet Oncol. 2018;19:370–381.
  • Yee AJ, Raje NS. Denosumab for the treatment of bone disease in solid tumors and multiple myeloma. Future Oncol. 2018;14:195–203.
  • Bolzoni M, Storti P, Bonomini S, et al. Immunomodulatory drugs lenalidomide and pomalidomide inhibit multiple myeloma-induced osteoclast formation and the RANKL/OPG ratio in the myeloma microenvironment targeting the expression of adhesion molecules. Exp Hematol. 2013;41:387–97 e1.
  • Breitkreutz I, Raab MS, Vallet S, et al. Lenalidomide inhibits osteoclastogenesis, survival factors and bone-remodeling markers in multiple myeloma. Leukemia. 2008;22:1925–1932.
  • Accardi F, Toscani D, Costa F, et al. The proteasome and myeloma-associated bone disease. Calcif Tissue Int. 2018;102:210–226.
  • Zavrski I, Krebbel H, Wildemann B, et al. Proteasome inhibitors abrogate osteoclast differentiation and osteoclast function. Biochem Biophys Res Commun. 2005;333:200–205.
  • Terpos E, Heath DJ, Rahemtulla A, et al. Bortezomib reduces serum dickkopf-1 and receptor activator of nuclear factor-kappaB ligand concentrations and normalises indices of bone remodelling in patients with relapsed multiple myeloma. Br J Haematol. 2006;135:688–692.
  • Ye H, Arron JR, Lamothe B, et al. Distinct molecular mechanism for initiating TRAF6 signalling. Nature. 2002;418:443–447.
  • Poblenz AT, Jacoby JJ, Singh S, et al. Inhibition of RANKL-mediated osteoclast differentiation by selective TRAF6 decoy peptides. Biochem Biophys Res Commun. 2007;359:510–515.
  • Chen H, Li M, Sanchez E, et al. Combined TRAF6 targeting and proteasome blockade has anti-myeloma and anti-bone resorptive effects. Mol Cancer Res. 2017;15:598–609.
  • Chen H, Li M, Campbell RA, et al. Interference with nuclear factor kappa B and c-Jun NH2-terminal kinase signaling by TRAF6C small interfering RNA inhibits myeloma cell proliferation and enhances apoptosis. Oncogene. 2006;25:6520–6527.
  • Ersek A, Xu K, Antonopoulos A, et al. Glycosphingolipid synthesis inhibition limits osteoclast activation and myeloma bone disease. J Clin Invest. 2015;125:2279–2292.
  • Hongming H, Jian H. Bortezomib inhibits maturation and function of osteoclasts from PBMCs of patients with multiple myeloma by downregulating TRAF6. Leuk Res. 2009;33:115–122.
  • Ang E, Pavlos NJ, Rea SL, et al. Proteasome inhibitors impair RANKL-induced NF-kappaB activity in osteoclast-like cells via disruption of p62, TRAF6, CYLD, and IkappaBalpha signaling cascades. J Cell Physiol. 2009;220:450–459.
  • Hiruma Y, Honjo T, Jelinek DF, et al. Increased signaling through p62 in the marrow microenvironment increases myeloma cell growth and osteoclast formation. Blood. 2009;113:4894–4902.
  • Teramachi J, Silbermann R, Yang P, et al. Blocking the ZZ domain of sequestosome1/p62 suppresses myeloma growth and osteoclast formation in vitro and induces dramatic bone formation in myeloma-bearing bones in vivo. Leukemia. 2016;30:390–398.
  • Hendriks RW, Yuvaraj S, Kil LP. Targeting Bruton’s tyrosine kinase in B cell malignancies. Nat Rev Cancer. 2014;14:219–232.
  • Shinohara M, Koga T, Okamoto K, et al. Tyrosine kinases Btk and Tec regulate osteoclast differentiation by linking RANK and ITAM signals. Cell. 2008;132:794–806.
  • Lee SH, Kim T, Jeong D, et al. The tec family tyrosine kinase Btk regulates RANKL-induced osteoclast maturation. J Biol Chem. 2008;283:11526–11534.
  • Bam R, Ling W, Khan S, et al. Role of Bruton’s tyrosine kinase in myeloma cell migration and induction of bone disease. Am J Hematol. 2013;88:463–471.
  • Tai YT, Chang BY, Kong SY, et al. Bruton tyrosine kinase inhibition is a novel therapeutic strategy targeting tumor in the bone marrow microenvironment in multiple myeloma. Blood. 2012;120:1877–1887.
  • Shinohara M, Chang BY, Buggy JJ, et al. The orally available Btk inhibitor ibrutinib (PCI-32765) protects against osteoclast-mediated bone loss. Bone. 2014;60:8–15.
  • Park JK, Byun JY, Park JA, et al. HM71224, a novel Bruton’s tyrosine kinase inhibitor, suppresses B cell and monocyte activation and ameliorates arthritis in a mouse model: a potential drug for rheumatoid arthritis. Arthritis Res Ther. 2016;18:91.
  • Pandey MK, Gowda K, Sung SS, et al. A novel dual inhibitor of microtubule and Bruton’s tyrosine kinase inhibits survival of multiple myeloma and osteoclastogenesis. Exp Hematol. 2017;53:31–42.
  • Eda H, Santo L, Cirstea DD, et al. A novel Bruton’s tyrosine kinase inhibitor CC-292 in combination with the proteasome inhibitor carfilzomib impacts the bone microenvironment in a multiple myeloma model with resultant antimyeloma activity. Leukemia. 2014;28:1892–1901.
  • Palma BD, Guasco D, Pedrazzoni M, et al. Osteolytic lesions, cytogenetic features and bone marrow levels of cytokines and chemokines in multiple myeloma patients: role of chemokine (C-C motif) ligand 20. Leukemia. 2016;30:409–416.
  • Giuliani N, Morandi F, Tagliaferri S, et al. Interleukin-3 (IL-3) is overexpressed by T lymphocytes in multiple myeloma patients. Blood. 2006;107:841–842.
  • Ray A, Das DS, Song Y, et al. A novel agent SL-401 induces anti-myeloma activity by targeting plasmacytoid dendritic cells, osteoclastogenesis and cancer stem-like cells. Leukemia. 2017;31:2652–2660.
  • Vallet S, Mukherjee S, Vaghela N, et al. Activin A promotes multiple myeloma-induced osteolysis and is a promising target for myeloma bone disease. Proc Natl Acad Sci U S A. 2010;107:5124–5129.
  • Raje N, Vallet S. Sotatercept, a soluble activin receptor type 2A IgG-Fc fusion protein for the treatment of anemia and bone loss. Curr Opin Mol Ther. 2010;12:586–597.
  • Ruckle J, Jacobs M, Kramer W, et al. Single-dose, randomized, double-blind, placebo-controlled study of ACE-011 (ActRIIA-IgG1) in postmenopausal women. J Bone Miner Res. 2009;24:744–752.
  • Abdulkadyrov KM, Salogub GN, Khuazheva NK, et al. Sotatercept in patients with osteolytic lesions of multiple myeloma. Br J Haematol. 2014;165:814–823.
  • Balkwill F, Mantovani A. Inflammation and cancer: back to Virchow? Lancet. 2001;357:539–545.
  • Mantovani A, Allavena P, Sica A, et al. Cancer-related inflammation. Nature. 2008;454:436–444.
  • Matthes T, Manfroi B, Huard B. Revisiting IL-6 antagonism in multiple myeloma. Crit Rev Oncol Hematol. 2016;105:1–4.
  • Orlowski RZ, Gercheva L, Williams C, et al. A phase 2, randomized, double-blind, placebo-controlled study of siltuximab (anti-IL-6 mAb) and bortezomib versus bortezomib alone in patients with relapsed or refractory multiple myeloma. Am J Hematol. 2015;90:42–49.
  • San-Miguel J, Blade J, Shpilberg O, et al. Phase 2 randomized study of bortezomib-melphalan-prednisone with or without siltuximab (anti-IL-6) in multiple myeloma. Blood. 2014;123:4136–4142.
  • Scheven BA, Milne JS, Hunter I, et al. Macrophage-inflammatory protein-1alpha regulates preosteoclast differentiation in vitro. Biochem Biophys Res Commun. 1999;254:773–778.
  • Oyajobi BO, Franchin G, Williams PJ, et al. Dual effects of macrophage inflammatory protein-1alpha on osteolysis and tumor burden in the murine 5TGM1 model of myeloma bone disease. Blood. 2003;102:311–319.
  • Han JH, Choi SJ, Kurihara N, et al. Macrophage inflammatory protein-1alpha is an osteoclastogenic factor in myeloma that is independent of receptor activator of nuclear factor kappaB ligand. Blood. 2001;97:3349–3353.
  • Choi SJ, Oba Y, Gazitt Y, et al. Antisense inhibition of macrophage inflammatory protein 1-alpha blocks bone destruction in a model of myeloma bone disease. J Clin Invest. 2001;108:1833–1841.
  • Vallet S, Pozzi S, Patel K, et al. A novel role for CCL3 (MIP-1alpha) in myeloma-induced bone disease via osteocalcin downregulation and inhibition of osteoblast function. Leukemia. 2011;25:1174–1181.
  • Giuliani N, Colla S, Sala R, et al. Human myeloma cells stimulate the receptor activator of nuclear factor-kappa B ligand (RANKL) in T lymphocytes: a potential role in multiple myeloma bone disease. Blood. 2002;100:4615–4621.
  • Weitzmann MN, Cenci S, Rifas L, et al. Interleukin-7 stimulates osteoclast formation by up-regulating the T-cell production of soluble osteoclastogenic cytokines. Blood. 2000;96:1873–1878.
  • Prabhala RH, Fulciniti M, Pelluru D, et al. Targeting IL-17A in multiple myeloma: a potential novel therapeutic approach in myeloma. Leukemia. 2016;30:379–389.
  • Ziegler-Heitbrock L. The CD14+ CD16+ blood monocytes: their role in infection and inflammation. J Leukoc Biol. 2007;81:584–592.
  • Chiu YG, Shao T, Feng C, et al. CD16 (FcRgammaIII) as a potential marker of osteoclast precursors in psoriatic arthritis. Arthritis Res Ther. 2010;12:R14.
  • Sponaas AM, Moen SH, Liabakk NB, et al. The proportion of CD16(+)CD14(dim) monocytes increases with tumor cell load in bone marrow of patients with multiple myeloma. Immun Inflamm Dis. 2015;3:94–102.
  • Petitprez V, Royer B, Desoutter J, et al. CD14+ CD16+ monocytes rather than CD14+ CD51/61+ monocytes are a potential cytological marker of circulating osteoclast precursors in multiple myeloma. A preliminary study. Int J Lab Hematol. 2015;37:29–35.
  • Bolzoni M, Ronchetti D, Storti P, et al. IL21R expressing CD14+CD16+ monocytes expand in multiple myeloma patients leading to increased osteoclasts. Haematologica. 2017;102:773–784.
  • Lokhorst HM, Plesner T, Laubach JP, et al. Targeting CD38 with daratumumab monotherapy in multiple myeloma. N Engl J Med. 2015;373:1207–1219.
  • Costa F, Toscani D, Chillemi A, et al. Expression of CD38 in myeloma bone niche: a rational basis for the use of anti-CD38 immunotherapy to inhibit osteoclast formation. Oncotarget. 2017;8:56598–56611.
  • An G, Acharya C, Feng X, et al. Osteoclasts promote immune suppressive microenvironment in multiple myeloma: therapeutic implication. Blood. 2016;128:1590–1603.
  • Faust J, Hunt P, Scully S, et al. Multiple myeloma cells and cells of the human osteoclast lineage share morphological and cell surface markers. J Cell Biochem. 1998;71:559–568.
  • Li Z, Rana TM. Therapeutic targeting of microRNAs: current status and future challenges. Nat Rev Drug Discov. 2014;13:622–638.
  • Lauressergues D, Couzigou JM, Clemente HS, et al. Primary transcripts of microRNAs encode regulatory peptides. Nature. 2015;520:90–93.
  • Sun W, Zhao C, Li Y, et al. Osteoclast-derived microRNA-containing exosomes selectively inhibit osteoblast activity. Cell Discov. 2016;2:16015.
  • Deng L, Wang Y, Peng Y, et al. Osteoblast-derived microvesicles: a novel mechanism for communication between osteoblasts and osteoclasts. Bone. 2015;79:37–42.
  • Huynh N, VonMoss L, Smith D, et al. Characterization of regulatory extracellular vesicles from osteoclasts. J Dent Res. 2016;95:673–679.
  • Ekstrom K, Omar O, Graneli C, et al. Monocyte exosomes stimulate the osteogenic gene expression of mesenchymal stem cells. PLoS One. 2013;8:e75227.
  • Omar OM, Graneli C, Ekstrom K, et al. The stimulation of an osteogenic response by classical monocyte activation. Biomaterials. 2011;32:8190–8204.
  • Raimondi L, De Luca A, Amodio N, et al. Involvement of multiple myeloma cell-derived exosomes in osteoclast differentiation. Oncotarget. 2015;6:13772–13789.
  • Shapiro IM, Landis WJ, Risbud MV. Matrix vesicles: are they anchored exosomes? Bone. 2015;79:29–36.
  • Li Q, Huang QP, Wang YL, et al. Extracellular vesicle-mediated bone metabolism in the bone microenvironment. J Bone Miner Metab. 2018;36:1–11.
  • Kagiya T, Nakamura S. Expression profiling of microRNAs in RAW264.7 cells treated with a combination of tumor necrosis factor alpha and RANKL during osteoclast differentiation. J Periodontal Res. 2013;48:373–385.
  • Fang J, Song XW, Tian J, et al. Overexpression of microRNA-378 attenuates ischemia-induced apoptosis by inhibiting caspase-3 expression in cardiac myocytes. Apoptosis. 2012;17:410–423.
  • Tsuchiya S, Fujiwara T, Sato F, et al. MicroRNA-210 regulates cancer cell proliferation through targeting fibroblast growth factor receptor-like 1 (FGFRL1). J Biol Chem. 2011;286:420–428.
  • Fasanaro P, Greco S, Lorenzi M, et al. An integrated approach for experimental target identification of hypoxia-induced miR-210. J Biol Chem. 2009;284:35134–35143.
  • Sugatani T, Hruska KA. MicroRNA-223 is a key factor in osteoclast differentiation. J Cell Biochem. 2007;101:996–999.
  • Sugatani T, Hruska KA. Impaired micro-RNA pathways diminish osteoclast differentiation and function. J Biol Chem. 2009;284:4667–4678.
  • Zhang J, Zhao H, Chen J, et al. Interferon-beta-induced miR-155 inhibits osteoclast differentiation by targeting SOCS1 and MITF. FEBS Lett. 2012;586:3255–3262.
  • Li D, Liu J, Guo B, et al. Osteoclast-derived exosomal miR-214-3p inhibits osteoblastic bone formation. Nat Commun. 2016;7:10872.
  • Rossi M, Pitari MR, Amodio N, et al. miR-29b negatively regulates human osteoclastic cell differentiation and function: implications for the treatment of multiple myeloma-related bone disease. J Cell Physiol. 2013;228:1506–1515.
  • Pitari MR, Rossi M, Amodio N, et al. Inhibition of miR-21 restores RANKL/OPG ratio in multiple myeloma-derived bone marrow stromal cells and impairs the resorbing activity of mature osteoclasts. Oncotarget. 2015;6:27343–27358.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.