nach oben

Calcified Tissue International

Erschienen in:

28.10.2017 | Review

The Proteasome and Myeloma-Associated Bone Disease

verfasst von: Fabrizio Accardi, Denise Toscani, Federica Costa, Franco Aversa, Nicola Giuliani

Erschienen in: Calcified Tissue International | Ausgabe 2/2018

Einloggen, um Zugang zu erhalten

Abstract

Bone disease is the hallmark of multiple myeloma (MM), a hematological malignancy characterized by osteolytic lesions due to a severe uncoupled and unbalanced bone remodeling with pronounced osteoblast suppression. Bone metastasis is also a frequent complication of solid tumors including advanced breast or prostate cancer. In the past years, the ubiquitin–proteasome pathway has been proved critical in regulating the balance between bone formation and bone resorption. Proteasome inhibitors (PIs) are a new class of drugs, currently used in the treatment of MM, that affect both tumor cells and bone microenvironment. Particularly, PIs stimulate osteoblast differentiation by human mesenchymal stromal cells and increase bone regeneration in mice. Interestingly, in vitro data indicate that PIs block MM-induced osteoblast and osteocyte cell death by targeting both apoptosis and autophagy. The preclinical data are supported by the following effects observed in MM patients treated with PIs: increase of bone alkaline phosphatase levels, normalization of the markers of bone turnover, and reduction of the skeletal-related events. Moreover, the histomorphometric data indicate that the treatment with bortezomib stimulates osteoblast formation and maintains osteocyte viability in MM patients. This review updates the evidence on the effects of PIs on bone remodeling and on cancer-induced bone disease while focusing on MM bone disease.

Mundy GR (2002) Metastasis to bone: causes, consequences and therapeutic opportunities. Nat Rev Cancer 2(8):584–593. doi:10.1038/nrc867 PubMedCrossRef

Roodman GD (2004) Pathogenesis of myeloma bone disease. Blood Cells Mol Dis 32(2):290–292. doi:10.1016/j.bcmd.2004.01.001 PubMedCrossRef

Coleman R, Gnant M, Morgan G, Clezardin P (2012) Effects of bone-targeted agents on cancer progression and mortality. J Natl Cancer Inst 104(14):1059–1067. doi:10.1093/jnci/djs263 PubMedCrossRef

Abdulkadyrov KM, Salogub GN, Khuazheva NK, Sherman ML, Laadem A, Barger R, Knight R, Srinivasan S, Terpos E (2014) Sotatercept in patients with osteolytic lesions of multiple myeloma. Br J Haematol 165(6):814–823. doi:10.1111/bjh.12835 PubMedPubMedCentralCrossRef

Fulciniti M, Tassone P, Hideshima T, Vallet S, Nanjappa P, Ettenberg SA, Shen Z, Patel N, Tai YT, Chauhan D, Mitsiades C, Prabhala R, Raje N, Anderson KC, Stover DR, Munshi NC (2009) Anti-DKK1 mAb (BHQ880) as a potential therapeutic agent for multiple myeloma. Blood 114(2):371–379. doi:10.1182/blood-2008-11-191577 PubMedPubMedCentralCrossRef

Heath DJ, Chantry AD, Buckle CH, Coulton L, Shaughnessy JD Jr, Evans HR, Snowden JA, Stover DR, Vanderkerken K, Croucher PI (2009) Inhibiting Dickkopf-1 (Dkk1) removes suppression of bone formation and prevents the development of osteolytic bone disease in multiple myeloma. J Bone Miner Res 24(3):425–436. doi:10.1359/jbmr.081104 PubMedCrossRef

Iyer SP, Beck JT, Stewart AK, Shah J, Kelly KR, Isaacs R, Bilic S, Sen S, Munshi NC (2014) A Phase IB multicentre dose-determination study of BHQ880 in combination with anti-myeloma therapy and zoledronic acid in patients with relapsed or refractory multiple myeloma and prior skeletal-related events. Br J Haematol 167(3):366–375. doi:10.1111/bjh.13056 PubMedCrossRef

Munshi NC, Abonour R, Beck JT, Bensinger W, Facon T, Stockerl-Goldstein K, Baz R, Siegel DS, Neben K, Lonial S (2012) Early evidence of anabolic bone activity of BHQ880, a fully human anti-DKK1 neutralizing antibody: results of a phase 2 study in previously untreated patients with smoldering multiple myeloma at risk for progression. Am Soc Hematol 120:331

Pennisi A, Ling W, Li X, Khan S, Wang Y, Barlogie B, Shaughnessy JD Jr, Yaccoby S (2010) Consequences of daily administered parathyroid hormone on myeloma growth, bone disease, and molecular profiling of whole myelomatous bone. PLoS ONE 5(12):e15233. doi:10.1371/journal.pone.0015233 PubMedPubMedCentralCrossRef

10.

Delgado-Calle J, Anderson J, Cregor MD, Condon KW, Kuhstoss SA, Plotkin LI, Bellido T, Roodman GD (2017) Genetic deletion of Sost or pharmacological inhibition of sclerostin prevent multiple myeloma-induced bone disease without affecting tumor growth. Leukemia. doi:10.1038/leu.2017.152 PubMedPubMedCentral

11.

McDonald MM, Reagan MR, Youlten SE, Mohanty ST, Seckinger A, Terry RL, Pettitt JA, Simic MK, Cheng TL, Morse A, Le LMT, Abi-Hanna D, Kramer I, Falank C, Fairfield H, Ghobrial IM, Baldock PA, Little DG, Kneissel M, Vanderkerken K, Bassett JHD, Williams GR, Oyajobi BO, Hose D, Phan TG, Croucher PI (2017) Inhibiting the osteocyte-specific protein sclerostin increases bone mass and fracture resistance in multiple myeloma. Blood 129(26):3452–3464. doi:10.1182/blood-2017-03-773341 PubMedPubMedCentralCrossRef

12.

Konstantinova IM, Tsimokha AS, Mittenberg AG (2008) Role of proteasomes in cellular regulation. Int Rev Cell Mol Biol 267:59–124. doi:10.1016/S1937-6448(08)00602-3 PubMedCrossRef

13.

Garrett IR, Chen D, Gutierrez G, Zhao M, Escobedo A, Rossini G, Harris SE, Gallwitz W, Kim KB, Hu S, Crews CM, Mundy GR (2003) Selective inhibitors of the osteoblast proteasome stimulate bone formation in vivo and in vitro. J Clin Invest 111(11):1771–1782. doi:10.1172/JCI16198 PubMedPubMedCentralCrossRef

14.

Teti A (2011) Bone development: overview of bone cells and signaling. Curr Osteoporos Rep 9(4):264–273. doi:10.1007/s11914-011-0078-8 PubMedCrossRef

15.

Yamashita M, Ying SX, Zhang GM, Li C, Cheng SY, Deng CX, Zhang YE (2005) Ubiquitin ligase Smurf1 controls osteoblast activity and bone homeostasis by targeting MEKK2 for degradation. Cell 121(1):101–113. doi:10.1016/j.cell.2005.01.035 PubMedPubMedCentralCrossRef

16.

Pan Y, Wang B (2007) A novel protein-processing domain in Gli2 and Gli3 differentially blocks complete protein degradation by the proteasome. J Biol Chem 282(15):10846–10852. doi:10.1074/jbc.M608599200 PubMedCrossRef

17.

Edwards CM, Edwards JR, Lwin ST, Esparza J, Oyajobi BO, McCluskey B, Munoz S, Grubbs B, Mundy GR (2008) Increasing Wnt signaling in the bone marrow microenvironment inhibits the development of myeloma bone disease and reduces tumor burden in bone in vivo. Blood 111(5):2833–2842. doi:10.1182/blood-2007-03-077685 PubMedPubMedCentralCrossRef

18.

Glickman MH, Ciechanover A (2002) The ubiquitin–proteasome proteolytic pathway: destruction for the sake of construction. Physiol Rev 82(2):373–428. doi:10.1152/physrev.00027.2001 PubMedCrossRef

19.

Coux O, Tanaka K, Goldberg AL (1996) Structure and functions of the 20S and 26S proteasomes. Annu Rev Biochem 65:801–847. doi:10.1146/annurev.bi.65.070196.004101 PubMedCrossRef

20.

Voges D, Zwickl P, Baumeister W (1999) The 26S proteasome: a molecular machine designed for controlled proteolysis. Annu Rev Biochem 68:1015–1068. doi:10.1146/annurev.biochem.68.1.1015 PubMedCrossRef

21.

Nakayama KI, Nakayama K (2006) Ubiquitin ligases: cell-cycle control and cancer. Nat Rev Cancer 6(5):369–381. doi:10.1038/nrc1881 PubMedCrossRef

22.

Giuliani N, Rizzoli V (2007) Myeloma cells and bone marrow osteoblast interactions: role in the development of osteolytic lesions in multiple myeloma. Leuk Lymphoma 48(12):2323–2329. doi:10.1080/10428190701648281 PubMedCrossRef

23.

Hadjidakis DJ, Androulakis II (2006) Bone remodeling. Ann N Y Acad Sci 1092:385–396. doi:10.1196/annals.1365.035 PubMedCrossRef

24.

Wilkinson KD (1995) Roles of ubiquitinylation in proteolysis and cellular regulation. Annu Rev Nutr 15:161–189. doi:10.1146/annurev.nu.15.070195.001113 PubMedCrossRef

25.

Deng ZL, Sharff KA, Tang N, Song WX, Luo J, Luo X, Chen J, Bennett E, Reid R, Manning D, Xue A, Montag AG, Luu HH, Haydon RC, He TC (2008) Regulation of osteogenic differentiation during skeletal development. Front Biosci 13:2001–2021PubMedCrossRef

26.

Wozney JM, Rosen V (1998) Bone morphogenetic protein and bone morphogenetic protein gene family in bone formation and repair. Clin Orthop Relat Res 346:26–37CrossRef

27.

Zhao M, Harris SE, Horn D, Geng Z, Nishimura R, Mundy GR, Chen D (2002) Bone morphogenetic protein receptor signaling is necessary for normal murine postnatal bone formation. J Cell Biol 157(6):1049–1060. doi:10.1083/jcb.200109012 PubMedPubMedCentralCrossRef

28.

Murray EJ, Bentley GV, Grisanti MS, Murray SS (1998) The ubiquitin–proteasome system and cellular proliferation and regulation in osteoblastic cells. Exp Cell Res 242(2):460–469. doi:10.1006/excr.1998.4090 PubMedCrossRef

29.

Zhao M, Qiao M, Harris SE, Oyajobi BO, Mundy GR, Chen D (2004) Smurf1 inhibits osteoblast differentiation and bone formation in vitro and in vivo. J Biol Chem 279(13):12854–12859. doi:10.1074/jbc.M313294200 PubMedCrossRef

30.

Jones DC, Wein MN, Oukka M, Hofstaetter JG, Glimcher MJ, Glimcher LH (2006) Regulation of adult bone mass by the zinc finger adapter protein Schnurri-3. Science 312(5777):1223–1227. doi:10.1126/science.1126313 PubMedCrossRef

31.

Hanai J, Chen LF, Kanno T, Ohtani-Fujita N, Kim WY, Guo WH, Imamura T, Ishidou Y, Fukuchi M, Shi MJ, Stavnezer J, Kawabata M, Miyazono K, Ito Y (1999) Interaction and functional cooperation of PEBP2/CBF with Smads. Synergistic induction of the immunoglobulin germline Calpha promoter. J Biol Chem 274(44):31577–31582PubMedCrossRef

32.

Chikazu D, Li X, Kawaguchi H, Sakuma Y, Voznesensky OS, Adams DJ, Xu M, Hoshio K, Katavic V, Herschman HR, Raisz LG, Pilbeam CC (2002) Bone morphogenetic protein 2 induces cyclo-oxygenase 2 in osteoblasts via a Cbfal binding site: role in effects of bone morphogenetic protein 2 in vitro and in vivo. J Bone Miner Res 17(8):1430–1440. doi:10.1359/jbmr.2002.17.8.1430 PubMedCrossRef

33.

Zhao M, Qiao M, Oyajobi BO, Mundy GR, Chen D (2003) E3 ubiquitin ligase Smurf1 mediates core-binding factor alpha1/Runx2 degradation and plays a specific role in osteoblast differentiation. J Biol Chem 278(30):27939–27944. doi:10.1074/jbc.M304132200 PubMedCrossRef

34.

Zhu H, Kavsak P, Abdollah S, Wrana JL, Thomsen GH (1999) A SMAD ubiquitin ligase targets the BMP pathway and affects embryonic pattern formation. Nature 400(6745):687–693. doi:10.1038/23293 PubMedCrossRef

35.

Jeon EJ, Lee KY, Choi NS, Lee MH, Kim HN, Jin YH, Ryoo HM, Choi JY, Yoshida M, Nishino N, Oh BC, Lee KS, Lee YH, Bae SC (2006) Bone morphogenetic protein-2 stimulates Runx2 acetylation. J Biol Chem 281(24):16502–16511. doi:10.1074/jbc.M512494200 PubMedCrossRef

36.

Kaneki H, Guo R, Chen D, Yao Z, Schwarz EM, Zhang YE, Boyce BF, Xing L (2006) Tumor necrosis factor promotes Runx2 degradation through up-regulation of Smurf1 and Smurf2 in osteoblasts. J Biol Chem 281(7):4326–4333. doi:10.1074/jbc.M509430200 PubMedCrossRef

37.

Zhao M, Qiao M, Harris SE, Chen D, Oyajobi BO, Mundy GR (2006) The zinc finger transcription factor Gli2 mediates bone morphogenetic protein 2 expression in osteoblasts in response to hedgehog signaling. Mol Cell Biol 26(16):6197–6208. doi:10.1128/MCB.02214-05 PubMedPubMedCentralCrossRef

38.

Jilka RL, O’Brien CA, Ali AA, Roberson PK, Weinstein RS, Manolagas SC (2009) Intermittent PTH stimulates periosteal bone formation by actions on post-mitotic preosteoblasts. Bone 44(2):275–286. doi:10.1016/j.bone.2008.10.037 PubMedCrossRef

39.

Jilka RL, Weinstein RS, Bellido T, Roberson P, Parfitt AM, Manolagas SC (1999) Increased bone formation by prevention of osteoblast apoptosis with parathyroid hormone. J Clin Invest 104(4):439–446. doi:10.1172/JCI6610 PubMedPubMedCentralCrossRef

40.

Bellido T, Ali AA, Plotkin LI, Fu Q, Gubrij I, Roberson PK, Weinstein RS, O’Brien CA, Manolagas SC, Jilka RL (2003) Proteasomal degradation of Runx2 shortens parathyroid hormone-induced anti-apoptotic signaling in osteoblasts. A putative explanation for why intermittent administration is needed for bone anabolism. J Biol Chem 278(50):50259–50272. doi:10.1074/jbc.M307444200 PubMedCrossRef

41.

Yang X, Karsenty G (2004) ATF4, the osteoblast accumulation of which is determined post-translationally, can induce osteoblast-specific gene expression in non-osteoblastic cells. J Biol Chem 279(45):47109–47114. doi:10.1074/jbc.M410010200 PubMedCrossRef

42.

Gaur T, Lengner CJ, Hovhannisyan H, Bhat RA, Bodine PV, Komm BS, Javed A, van Wijnen AJ, Stein JL, Stein GS, Lian JB (2005) Canonical WNT signaling promotes osteogenesis by directly stimulating Runx2 gene expression. J Biol Chem 280(39):33132–33140. doi:10.1074/jbc.M500608200 PubMedCrossRef

43.

Mercurio F, Manning AM (1999) Multiple signals converging on NF-kappaB. Curr Opin Cell Biol 11(2):226–232PubMedCrossRef

44.

Lomaga MA, Yeh WC, Sarosi I, Duncan GS, Furlonger C, Ho A, Morony S, Capparelli C, Van G, Kaufman S, van der Heiden A, Itie A, Wakeham A, Khoo W, Sasaki T, Cao Z, Penninger JM, Paige CJ, Lacey DL, Dunstan CR, Boyle WJ, Goeddel DV, Mak TW (1999) TRAF6 deficiency results in osteopetrosis and defective interleukin-1, CD40, and LPS signaling. Genes Dev 13(8):1015–1024PubMedPubMedCentralCrossRef

45.

Lamothe B, Besse A, Campos AD, Webster WK, Wu H, Darnay BG (2007) Site-specific Lys-63-linked tumor necrosis factor receptor-associated factor 6 auto-ubiquitination is a critical determinant of I kappa B kinase activation. J Biol Chem 282(6):4102–4112. doi:10.1074/jbc.M609503200 PubMedCrossRef

46.

Chen H, Li M, Sanchez E, Wang CS, Lee T, Soof CM, Casas CE, Cao J, Xie C, Udd KA, DeCorso K, Tang GY, Spektor TM, Berenson JR (2017) Combined TRAF6 targeting and proteasome blockade has anti-tumor and anti-bone resorptive effects. Mol Cancer Res. doi:10.1158/1541-7786.MCR-16-0293

47.

Tan EM, Li L, Indran IR, Chew N, Yong EL (2016) TRAF6 mediates suppression of osteoclastogenesis and prevention of ovariectomy-induced bone loss by a novel prenylflavonoid. J Bone Miner Res. doi:10.1002/jbmr.3031

48.

Yang XD, Sun SC (2015) Targeting signaling factors for degradation, an emerging mechanism for TRAF functions. Immunol Rev 266(1):56–71. doi:10.1111/imr.12311 PubMedPubMedCentralCrossRef

49.

Novack DV, Yin L, Hagen-Stapleton A, Schreiber RD, Goeddel DV, Ross FP, Teitelbaum SL (2003) The IkappaB function of NF-kappaB2 p100 controls stimulated osteoclastogenesis. J Exp Med 198(5):771–781. doi:10.1084/jem.20030116 PubMedPubMedCentralCrossRef

50.

Landis-Piwowar KR, Milacic V, Chen D, Yang H, Zhao Y, Chan TH, Yan B, Dou QP (2006) The proteasome as a potential target for novel anticancer drugs and chemosensitizers. Drug Resist Updat 9(6):263–273. doi:10.1016/j.drup.2006.11.001 PubMedCrossRef

51.

Kubiczkova L, Pour L, Sedlarikova L, Hajek R, Sevcikova S (2014) Proteasome inhibitors—molecular basis and current perspectives in multiple myeloma. J Cell Mol Med 18(6):947–961. doi:10.1111/jcmm.12279 PubMedPubMedCentralCrossRef

52.

Richardson PG, Mitsiades C, Schlossman R, Ghobrial I, Hideshima T, Munshi N, Anderson KC (2008) Bortezomib in the front-line treatment of multiple myeloma. Expert Rev Anticancer Ther 8(7):1053–1072. doi:10.1586/14737140.8.7.1053 PubMedCrossRef

53.

Groll M, Berkers CR, Ploegh HL, Ovaa H (2006) Crystal structure of the boronic acid-based proteasome inhibitor bortezomib in complex with the yeast 20S proteasome. Structure 14(3):451–456. doi:10.1016/j.str.2005.11.019 PubMedCrossRef

54.

Elliot PJ, Adams J (1999) Recent advances in understanding proteasome function. Curr Opin Drug Discov Dev 2(5):484–490

55.

Obeng EA, Carlson LM, Gutman DM, Harrington WJ Jr, Lee KP, Boise LH (2006) Proteasome inhibitors induce a terminal unfolded protein response in multiple myeloma cells. Blood 107(12):4907–4916. doi:10.1182/blood-2005-08-3531 PubMedPubMedCentralCrossRef

56.

Orlowski RZ, Kuhn DJ (2008) Proteasome inhibitors in cancer therapy: lessons from the first decade. Clin Cancer Res 14(6):1649–1657. doi:10.1158/1078-0432.CCR-07-2218 PubMedCrossRef

57.

Richardson PG, Briemberg H, Jagannath S, Wen PY, Barlogie B, Berenson J, Singhal S, Siegel DS, Irwin D, Schuster M, Srkalovic G, Alexanian R, Rajkumar SV, Limentani S, Alsina M, Orlowski RZ, Najarian K, Esseltine D, Anderson KC, Amato AA (2006) Frequency, characteristics, and reversibility of peripheral neuropathy during treatment of advanced multiple myeloma with bortezomib. J Clin Oncol 24(19):3113–3120. doi:10.1200/JCO.2005.04.7779 PubMedCrossRef

58.

Kupperman E, Lee EC, Cao Y, Bannerman B, Fitzgerald M, Berger A, Yu J, Yang Y, Hales P, Bruzzese F, Liu J, Blank J, Garcia K, Tsu C, Dick L, Fleming P, Yu L, Manfredi M, Rolfe M, Bolen J (2010) Evaluation of the proteasome inhibitor MLN9708 in preclinical models of human cancer. Cancer Res 70(5):1970–1980. doi:10.1158/0008-5472.CAN-09-2766 PubMedCrossRef

59.

Garcia-Gomez A, Quwaider D, Canavese M, Ocio EM, Tian Z, Blanco JF, Berger AJ, Ortiz-de-Solorzano C, Hernandez-Iglesias T, Martens AC, Groen RW, Mateo-Urdiales J, Fraile S, Galarraga M, Chauhan D, San Miguel JF, Raje N, Garayoa M (2014) Preclinical activity of the oral proteasome inhibitor MLN9708 in Myeloma bone disease. Clin Cancer Res 20(6):1542–1554. doi:10.1158/1078-0432.CCR-13-1657 PubMedCrossRef

60.

Lee EC, Fitzgerald M, Bannerman B, Donelan J, Bano K, Terkelsen J, Bradley DP, Subakan O, Silva MD, Liu R, Pickard M, Li Z, Tayber O, Li P, Hales P, Carsillo M, Neppalli VT, Berger AJ, Kupperman E, Manfredi M, Bolen JB, Van Ness B, Janz S (2011) Antitumor activity of the investigational proteasome inhibitor MLN9708 in mouse models of B-cell and plasma cell malignancies. Clin Cancer Res 17(23):7313–7323. doi:10.1158/1078-0432.CCR-11-0636 PubMedPubMedCentralCrossRef

61.

Piva R, Ruggeri B, Williams M, Costa G, Tamagno I, Ferrero D, Giai V, Coscia M, Peola S, Massaia M, Pezzoni G, Allievi C, Pescalli N, Cassin M, di Giovine S, Nicoli P, de Feudis P, Strepponi I, Roato I, Ferracini R, Bussolati B, Camussi G, Jones-Bolin S, Hunter K, Zhao H, Neri A, Palumbo A, Berkers C, Ovaa H, Bernareggi A, Inghirami G (2008) CEP-18770: a novel, orally active proteasome inhibitor with a tumor-selective pharmacologic profile competitive with bortezomib. Blood 111(5):2765–2775. doi:10.1182/blood-2007-07-100651 PubMedCrossRef

62.

Meng L, Mohan R, Kwok BH, Elofsson M, Sin N, Crews CM (1999) Epoxomicin, a potent and selective proteasome inhibitor, exhibits in vivo antiinflammatory activity. Proc Natl Acad Sci USA 96(18):10403–10408PubMedPubMedCentralCrossRef

63.

Demo SD, Kirk CJ, Aujay MA, Buchholz TJ, Dajee M, Ho MN, Jiang J, Laidig GJ, Lewis ER, Parlati F, Shenk KD, Smyth MS, Sun CM, Vallone MK, Woo TM, Molineaux CJ, Bennett MK (2007) Antitumor activity of PR-171, a novel irreversible inhibitor of the proteasome. Cancer Res 67(13):6383–6391. doi:10.1158/0008-5472.CAN-06-4086 PubMedCrossRef

64.

O’Connor OA, Stewart AK, Vallone M, Molineaux CJ, Kunkel LA, Gerecitano JF, Orlowski RZ (2009) A phase 1 dose escalation study of the safety and pharmacokinetics of the novel proteasome inhibitor carfilzomib (PR-171) in patients with hematologic malignancies. Clin Cancer Res 15(22):7085–7091. doi:10.1158/1078-0432.CCR-09-0822 PubMedPubMedCentralCrossRef

65.

Kuhn DJ, Chen Q, Voorhees PM, Strader JS, Shenk KD, Sun CM, Demo SD, Bennett MK, van Leeuwen FW, Chanan-Khan AA, Orlowski RZ (2007) Potent activity of carfilzomib, a novel, irreversible inhibitor of the ubiquitin–proteasome pathway, against preclinical models of multiple myeloma. Blood 110(9):3281–3290. doi:10.1182/blood-2007-01-065888 PubMedPubMedCentralCrossRef

66.

Chauhan D, Catley L, Li G, Podar K, Hideshima T, Velankar M, Mitsiades C, Mitsiades N, Yasui H, Letai A, Ovaa H, Berkers C, Nicholson B, Chao TH, Neuteboom ST, Richardson P, Palladino MA, Anderson KC (2005) A novel orally active proteasome inhibitor induces apoptosis in multiple myeloma cells with mechanisms distinct from Bortezomib. Cancer Cell 8(5):407–419. doi:10.1016/j.ccr.2005.10.013 PubMedCrossRef

67.

Potts BC, Albitar MX, Anderson KC, Baritaki S, Berkers C, Bonavida B, Chandra J, Chauhan D, Cusack JC Jr, Fenical W, Ghobrial IM, Groll M, Jensen PR, Lam KS, Lloyd GK, McBride W, McConkey DJ, Miller CP, Neuteboom ST, Oki Y, Ovaa H, Pajonk F, Richardson PG, Roccaro AM, Sloss CM, Spear MA, Valashi E, Younes A, Palladino MA (2011) Marizomib, a proteasome inhibitor for all seasons: preclinical profile and a framework for clinical trials. Curr Cancer Drug Targets 11(3):254–284PubMedPubMedCentralCrossRef

68.

Peng X, Guo W, Ren T, Lou Z, Lu X, Zhang S, Lu Q, Sun Y (2013) Differential expression of the RANKL/RANK/OPG system is associated with bone metastasis in human non-small cell lung cancer. PLoS ONE 8(3):e58361. doi:10.1371/journal.pone.0058361 PubMedPubMedCentralCrossRef

69.

Chen G, Sircar K, Aprikian A, Potti A, Goltzman D, Rabbani SA (2006) Expression of RANKL/RANK/OPG in primary and metastatic human prostate cancer as markers of disease stage and functional regulation. Cancer 107(2):289–298. doi:10.1002/cncr.21978 PubMedCrossRef

70.

Canon JR, Roudier M, Bryant R, Morony S, Stolina M, Kostenuik PJ, Dougall WC (2008) Inhibition of RANKL blocks skeletal tumor progression and improves survival in a mouse model of breast cancer bone metastasis. Clin Exp Metastasis 25(2):119–129. doi:10.1007/s10585-007-9127-1 PubMedCrossRef

71.

Hall CL, Daignault SD, Shah RB, Pienta KJ, Keller ET (2008) Dickkopf-1 expression increases early in prostate cancer development and decreases during progression from primary tumor to metastasis. Prostate 68(13):1396–1404. doi:10.1002/pros.20805 PubMedPubMedCentralCrossRef

72.

Sanvoranart T, Supokawej A, Kheolamai P, U-Pratya Y, Klincumhom N, Manochantr S, Wattanapanitch M, Issaragrisil S (2014) Bortezomib enhances the osteogenic differentiation capacity of human mesenchymal stromal cells derived from bone marrow and placental tissues. Biochem Biophys Res Commun 447(4):580–585. doi:10.1016/j.bbrc.2014.04.044 PubMedCrossRef

73.

Giuliani N, Morandi F, Tagliaferri S, Lazzaretti M, Bonomini S, Crugnola M, Mancini C, Martella E, Ferrari L, Tabilio A, Rizzoli V (2007) The proteasome inhibitor bortezomib affects osteoblast differentiation in vitro and in vivo in multiple myeloma patients. Blood 110(1):334–338. doi:10.1182/blood-2006-11-059188 PubMedCrossRef

74.

Mukherjee S, Raje N, Schoonmaker JA, Liu JC, Hideshima T, Wein MN, Jones DC, Vallet S, Bouxsein ML, Pozzi S, Chhetri S, Seo YD, Aronson JP, Patel C, Fulciniti M, Purton LE, Glimcher LH, Lian JB, Stein G, Anderson KC, Scadden DT (2008) Pharmacologic targeting of a stem/progenitor population in vivo is associated with enhanced bone regeneration in mice. J Clin Invest 118(2):491–504. doi:10.1172/JCI33102 PubMedPubMedCentral

75.

Qiang YW, Hu B, Chen Y, Zhong Y, Shi B, Barlogie B, Shaughnessy JD Jr (2009) Bortezomib induces osteoblast differentiation via Wnt-independent activation of beta-catenin/TCF signaling. Blood 113(18):4319–4330. doi:10.1182/blood-2008-08-174300 PubMedPubMedCentralCrossRef

76.

Uyama M, Sato MM, Kawanami M, Tamura M (2012) Regulation of osteoblastic differentiation by the proteasome inhibitor bortezomib. Genes Cells 17(7):548–558. doi:10.1111/j.1365-2443.2012.01611.x PubMedCrossRef

77.

Oyajobi BO, Garrett IR, Gupta A, Flores A, Esparza J, Munoz S, Zhao M, Mundy GR (2007) Stimulation of new bone formation by the proteasome inhibitor, bortezomib: implications for myeloma bone disease. Br J Haematol 139(3):434–438. doi:10.1111/j.1365-2141.2007.06829.x PubMedPubMedCentralCrossRef

78.

Pennisi A, Li X, Ling W, Khan S, Zangari M, Yaccoby S (2009) The proteasome inhibitor, bortezomib suppresses primary myeloma and stimulates bone formation in myelomatous and nonmyelomatous bones in vivo. Am J Hematol 84(1):6–14. doi:10.1002/ajh.21310 PubMedPubMedCentralCrossRef

79.

Deleu S, Lemaire M, Arts J, Menu E, Van Valckenborgh E, Vande Broek I, De Raeve H, Coulton L, Van Camp B, Croucher P, Vanderkerken K (2009) Bortezomib alone or in combination with the histone deacetylase inhibitor JNJ-26481585: effect on myeloma bone disease in the 5T2MM murine model of myeloma. Cancer Res 69(13):5307–5311. doi:10.1158/0008-5472.CAN-08-4472 PubMedCrossRef

80.

Kaiser MF, Heider U, Mieth M, Zang C, von Metzler I, Sezer O (2013) The proteasome inhibitor bortezomib stimulates osteoblastic differentiation of human osteoblast precursors via upregulation of vitamin D receptor signalling. Eur J Haematol 90(4):263–272. doi:10.1111/ejh.12069 PubMedCrossRef

81.

Hurchla MA, Garcia-Gomez A, Hornick MC, Ocio EM, Li A, Blanco JF, Collins L, Kirk CJ, Piwnica-Worms D, Vij R, Tomasson MH, Pandiella A, San Miguel JF, Garayoa M, Weilbaecher KN (2013) The epoxyketone-based proteasome inhibitors carfilzomib and orally bioavailable oprozomib have anti-resorptive and bone-anabolic activity in addition to anti-myeloma effects. Leukemia 27(2):430–440. doi:10.1038/leu.2012.183 PubMedCrossRef

82.

Hu B, Chen Y, Usmani SZ, Ye S, Qiang W, Papanikolaou X, Heuck CJ, Yaccoby S, Williams BO, Van Rhee F, Barlogie B, Epstein J, Qiang YW (2013) Characterization of the molecular mechanism of the bone-anabolic activity of carfilzomib in multiple myeloma. PLoS ONE 8(9):e74191. doi:10.1371/journal.pone.0074191 PubMedPubMedCentralCrossRef

83.

Li Y, Li J, Zhuang W, Wang Q, Ge X, Zhang X, Chen P, Fu J, Li B (2014) Carfilzomib promotes the osteogenic differentiation potential of mesenchymal stem cells derived from myeloma patients by inhibiting notch1 activity in vitro. Leuk Res 38(8):970–976. doi:10.1016/j.leukres.2014.05.022 PubMedCrossRef

84.

Hilton MJ, Tu X, Wu X, Bai S, Zhao H, Kobayashi T, Kronenberg HM, Teitelbaum SL, Ross FP, Kopan R, Long F (2008) Notch signaling maintains bone marrow mesenchymal progenitors by suppressing osteoblast differentiation. Nat Med 14(3):306–314. doi:10.1038/nm1716 PubMedPubMedCentralCrossRef

85.

Bonewald LF (2011) The amazing osteocyte. J Bone Miner Res 26(2):229–238. doi:10.1002/jbmr.320 PubMedCrossRef

86.

Giuliani N, Ferretti M, Bolzoni M, Storti P, Lazzaretti M, Dalla Palma B, Bonomini S, Martella E, Agnelli L, Neri A, Ceccarelli F, Palumbo C (2012) Increased osteocyte death in multiple myeloma patients: role in myeloma-induced osteoclast formation. Leukemia 26(6):1391–1401. doi:10.1038/leu.2011.381 PubMedCrossRef

87.

Toscani D, Palumbo C, Dalla Palma B, Ferretti M, Bolzoni M, Marchica V, Sena P, Martella E, Mancini C, Ferri V, Costa F, Accardi F, Craviotto L, Aversa F, Giuliani N (2016) The proteasome inhibitor bortezomib maintains osteocyte viability in multiple myeloma patients by reducing both apoptosis and autophagy: a new function for proteasome inhibitors. J Bone Miner Res 31(4):815–827. doi:10.1002/jbmr.2741 PubMedCrossRef

88.

Staines KA, Prideaux M, Allen S, Buttle DJ, Pitsillides AA, Farquharson C (2016) E11/podoplanin protein stabilization through inhibition of the proteasome promotes osteocyte differentiation in murine in vitro models. J Cell Physiol 231(6):1392–1404. doi:10.1002/jcp.25282 PubMedCrossRef

89.

Jones MD, Liu JC, Barthel TK, Hussain S, Lovria E, Cheng D, Schoonmaker JA, Mulay S, Ayers DC, Bouxsein ML, Stein GS, Mukherjee S, Lian JB (2010) A proteasome inhibitor, bortezomib, inhibits breast cancer growth and reduces osteolysis by downregulating metastatic genes. Clin Cancer Res 16(20):4978–4989. doi:10.1158/1078-0432.CCR-09-3293 PubMedPubMedCentralCrossRef

90.

Wang Z, Wang J, Li X, Xing L, Ding Y, Shi P, Zhang Y, Guo S, Shu X, Shan B (2014) Bortezomib prevents oncogenesis and bone metastasis of prostate cancer by inhibiting WWP1, Smurf1 and Smurf2. Int J Oncol 45(4):1469–1478. doi:10.3892/ijo.2014.2545 PubMedCrossRef

91.

Whang PG, Gamradt SC, Gates JJ, Lieberman JR (2005) Effects of the proteasome inhibitor bortezomib on osteolytic human prostate cancer cell metastases. Prostate Cancer Prostatic Dis 8(4):327–334. doi:10.1038/sj.pcan.4500823 PubMedCrossRef

92.

Teicher BA, Anderson KC (2015) CCR 20th anniversary commentary: in the beginning, there was PS-341. Clin Cancer Res 21(5):939–941PubMedPubMedCentralCrossRef

93.

Zangari M, Esseltine D, Lee CK, Barlogie B, Elice F, Burns MJ, Kang SH, Yaccoby S, Najarian K, Richardson P (2005) Response to bortezomib is associated to osteoblastic activation in patients with multiple myeloma. Br J Haematol 131(1):71–73PubMedCrossRef

94.

Zangari M, Esseltine D, Cavallo F, Neuwirth R, Elice F, Burns MJ, Yaccoby S, Richardson P, Sonneveld P, Tricot G (2007) Predictive value of alkaline phosphatase for response and time to progression in bortezomib-treated multiple myeloma patients. Am J Hematol 82(9):831–833PubMedCrossRef

95.

Terpos E, Heath DJ, Rahemtulla A, Zervas K, Chantry A, Anagnostopoulos A, Pouli A, Katodritou E, Verrou E, Vervessou EC (2006) Bortezomib reduces serum dickkopf-1 and receptor activator of nuclear factor-κB ligand concentrations and normalises indices of bone remodelling in patients with relapsed multiple myeloma. Br J Haematol 135(5):688–692PubMedCrossRef

96.

Boissy P, Andersen TL, Lund T, Kupisiewicz K, Plesner T, Delaisse JM (2008) Pulse treatment with the proteasome inhibitor bortezomib inhibits osteoclast resorptive activity in clinically relevant conditions. Leuk Res 32(11):1661–1668PubMedCrossRef

97.

Lund T, Søe K, Abildgaard N, Garnero P, Pedersen PT, Ormstrup T, Delaissé JM, Plesner T (2010) First-line treatment with bortezomib rapidly stimulates both osteoblast activity and bone matrix deposition in patients with multiple myeloma, and stimulates osteoblast proliferation and differentiation in vitro. Eur J Haematol 85(4):290–299PubMedPubMedCentralCrossRef

98.

Zangari M, Yaccoby S, Pappas L, Cavallo F, Kumar NS, Ranganathan S, Suva LJ, Gruenwald JM, Kern S, Zhan F (2011) A prospective evaluation of the biochemical, metabolic, hormonal and structural bone changes associated with bortezomib response in multiple myeloma patients. Haematologica 96(2):333–336PubMedCrossRef

99.

Delforge M, Terpos E, Richardson PG, Shpilberg O, Khuageva NK, Schlag R, Dimopoulos MA, Kropff M, Spicka I, Petrucci MT (2011) Fewer bone disease events, improvement in bone remodeling, and evidence of bone healing with bortezomib plus melphalan–prednisone vs. melphalan–prednisone in the phase III VISTA trial in multiple myeloma. Eur J Haematol 86(5):372–384PubMedCrossRef

100.

Terpos E, Christoulas D, Kastritis E, Katodritou E, Papatheodorou A, Pouli A, Kyrtsonis MC, Michalis E, Papanikolaou X, Gkotzamanidou M (2014) The combination of lenalidomide and dexamethasone reduces bone resorption in responding patients with relapsed/refractory multiple myeloma but has no effect on bone formation: final results on 205 patients of the Greek myeloma study group. Am J Hematol 89(1):34–40PubMedCrossRef

101.

Uy GL, Trivedi R, Peles S, Fisher NM, Zhang QJ, Tomasson MH, DiPersio JF, Vij R (2007) Bortezomib inhibits osteoclast activity in patients with multiple myeloma. Clin Lymphoma Myeloma 7(9):587–589PubMedCrossRef

102.

Terpos E, Christoulas D, Kastritis E, Roussou M, Migkou M, Eleutherakis-Papaiakovou E, Gavriatopoulou M, Gkotzamanidou M, Kanellias N, Manios E (2014) VTD consolidation, without bisphosphonates, reduces bone resorption and is associated with a very low incidence of skeletal-related events in myeloma patients post ASCT. Leukemia 28(4):928–934PubMedCrossRef

103.

Zangari M, Aujay M, Zhan F, Hetherington KL, Berno T, Vij R, Jagannath S, Siegel D, Keith Stewart A, Wang L (2011) Alkaline phosphatase variation during carfilzomib treatment is associated with best response in multiple myeloma patients. Eur J Haematol 86(6):484–487PubMedCrossRef

104.

Lee SE, Min CK, Yahng SA, Cho BS, Eom KS, Kim YJ, Kim HJ, Lee S, Cho SG, Kim DW (2011) Bone scan images reveal increased osteoblastic function after bortezomib treatment in patients with multiple myeloma. Eur J Haematol 86(1):83–86PubMedCrossRef

105.

Terpos E, Christoulas D, Kokkoris P, Anargyrou K, Gavriatopoulou M, Migkou M, Tsionos K, Dimopoulos MA (2010) Increased bone mineral density in a subset of patients with relapsed multiple myeloma who received the combination of bortezomib, dexamethasone and zoledronic acid. Ann Oncol 21(7):1561–1562PubMedCrossRef

106.

Zangari M, Berno T, Salama ME, Sana S, Talamo G, Pena K, Miller S, Zhan F (2013) Effect of low dose bortezomib on bone formation in smoldering myeloma patients. Blood 122(21):3204

107.

Schulze M, Weisel K, Grandjean C, Oehrlein K, Zago M, Spira D, Horger M (2014) Increasing bone sclerosis during bortezomib therapy in multiple myeloma patients: results of a reduced-dose whole-body MDCT study. Am J Roentgenol 202(1):170–179CrossRef

108.

Hinge M, Andersen KT, Lund T, Jørgensen HB, Holdgaard PC, Ormstrup TE, Østergaard LL, Plesner T (2016) Bone healing in multiple myeloma: a prospective evaluation of the impact of first-line anti-myeloma treatment. Haematologica 101(10):e419PubMedPubMedCentralCrossRef

Titel: The Proteasome and Myeloma-Associated Bone Disease
verfasst von: Fabrizio Accardi
Denise Toscani
Federica Costa
Franco Aversa
Nicola Giuliani
Publikationsdatum: 28.10.2017
Verlag: Springer US
Erschienen in: Calcified Tissue International / Ausgabe 2/2018
Print ISSN: 0171-967X
Elektronische ISSN: 1432-0827
DOI: https://doi.org/10.1007/s00223-017-0349-1

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Innere Medizin

25.04.2024 | Hypotonie | Nachrichten

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

The Proteasome and Myeloma-Associated Bone Disease

Abstract

Leitlinien kompakt für die Innere Medizin

Neu im Fachgebiet Innere Medizin

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

Viel Bewegung in der Parkinsonforschung

Adjuvante Immuntherapie verlängert Leben bei RCC

Update Innere Medizin

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 2/2018

New agents in the Treatment of Myeloma Bone Disease

Osteomimicry: How the Seed Grows in the Soil

Bone-Targeted Therapies in Cancer-Induced Bone Disease

Recent Trends and Advances in Cancer-Induced Bone Disease

Bone Marrow Microenvironment as a Regulator and Therapeutic Target for Prostate Cancer Bone Metastasis

Cancer Treatment and Bone Health

Leitlinien kompakt für die Innere Medizin

Neu im Fachgebiet Innere Medizin

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

Viel Bewegung in der Parkinsonforschung

Adjuvante Immuntherapie verlängert Leben bei RCC

Update Innere Medizin