1,112
Views
7
CrossRef citations to date
0
Altmetric
Research Paper

Anti-myeloma effect of pharmacological inhibition of Notch/gamma-secretase with RO4929097 is mediated by modulation of tumor microenvironment

, , , , &
Pages 477-485 | Received 07 Oct 2015, Accepted 14 Feb 2016, Published online: 11 Apr 2016

References

  • Nefedova Y, Cheng P, Alsina M, Dalton W, Gabrilovich D. Involvement of Notch-1 signaling in bone marrow stroma-mediated de novo drug resistance of myeloma and other malignant lymphoid cell lines. Blood 2004; 103:3503-10; PMID:14670925; http://dx.doi.org/10.1182/blood-2003-07-2340
  • Schwarzer R, Kaiser M, Acikgoez O, Heider U, Mathas S, Preissner R, Sezer O, Doerken B, Jundt F. Notch inhibition blocks multiple myeloma cell-induced osteoclast activation. Leukemia 2008; 12:2273-7; PMID:18528422; http://dx.doi.org/10.1038/leu.2008.138
  • Jundt F, Probsting KS, Anagnostopoulos I, Muehlinghaus G, Chatterjee M, Mathas S, Bargou RC, Manz R, Stein H, Dorken B. Jagged1-induced Notch signaling drives proliferation of multiple myeloma cells. Blood 2004; 103:3511-5; PMID:14726396; http://dx.doi.org/10.1182/blood-2003-07-2254
  • Sethi N, Dai X, Winter C, Kang Y. Tumor-derived JAGGED1 promotes osteolytic bone metastasis of breast cancer by engaging notch signaling in bone cells. Cancer Cell 2011; 19:192-205; PMID:21295524; http://dx.doi.org/10.1016/j.ccr.2010.12.022
  • Osborne B, Miele L. Notch and the immune system. Immunity 1999; 11:653-63; PMID:10626888; http://dx.doi.org/10.1016/S1074-7613(00)80140-5
  • Kopan R, Goate A. A common enzyme connects notch signaling and Alzheimer's disease. Genes Dev 2000; 14:2799-806; PMID:11090127; http://dx.doi.org/10.1101/gad.836900
  • Yu G, Nishimura M, Arawaka S, Levitan D, Zhang L, Tandon A, Song YQ, Rogaeva E, Chen F, Kawarai T, et al. Nicastrin modulates presenilin-mediated notch/glp-1 signal transduction and betaAPP processing. Nature 2000; 407:48-54; PMID:10993067; http://dx.doi.org/10.1038/35024009
  • Maier M, Gessler M. Comparative analysis of the human and mouse Hey1 promoter: hey genes are new Notch target genes. Biochem Biophys Res Commun 2000; 275:652-60; PMID:10964718; http://dx.doi.org/10.1006/bbrc.2000.3354
  • Jarriault S, Brou C, Logeat F, Schroeter E, Kopan R, Israel A. Signalling downstream of activated mammalian Notch. Nature 1995; 377:355-8; PMID:7566092; http://dx.doi.org/10.1038/377355a0
  • Weng A, Millholland J, Yashiro-Ohtani Y, Arcangeli M, Lau A, Wai C, Del Bianco C, Rodriguez C, Sai H, Tobias J, et al. c-Myc is an important direct target of Notch1 in T-cell acute lymphoblastic leukemia/lymphoma. Genes Dev 2006; 20:2096-109; PMID:16847353; http://dx.doi.org/10.1101/gad.1450406
  • Ronchini C, Capobianco A. Induction of cyclin D1 transcription and CDK2 activity by Notch(ic): implication for cell cycle disruption in transformation by Notch(ic). Mol Cell Biol 2001; 21:5925-34; PMID:11486031; http://dx.doi.org/10.1128/MCB.21.17.5925-5934.2001
  • Luistro L, He W, Smith M, Packman K, Vilenchik M, Carvajal D, Roberts J, Cai J, Berkofsky-Fessler W, Hilton H, et al. Preclinical profile of a potent gamma-secretase inhibitor targeting notch signaling with in vivo efficacy and pharmacodynamic properties. Cancer Res 2009; 69:7672-80; PMID:19773430; http://dx.doi.org/10.1158/0008-5472.CAN-09-1843
  • Huynh C, Poliseno L, Segura M, Medicherla R, Haimovic A, Menendez S, Shang S, Pavlick A, Shao Y, Darvishian F, et al. The novel gamma secretase inhibitor RO4929097 reduces the tumor initiating potential of melanoma. PLoS One 2011; 6:e25264; PMID:21980408; http://dx.doi.org/10.1371/journal.pone.0025264
  • Diaz-Padilla I, Wilson M, Clarke B, Hirte H, Welch S, Mackay H, Biagi J, Reedijk M, Weberpals J, Fleming G, et al. A phase II study of single-agent RO4929097, a gamma-secretase inhibitor of Notch signaling, in patients with recurrent platinum-resistant epithelial ovarian cancer: a study of the Princess Margaret, Chicago and California phase II consortia. Gynecol Oncol 2015; 137:216-22; PMID:25769658; http://dx.doi.org/10.1016/j.ygyno.2015.03.005
  • Lee S, Moon J, Redman B, Chidiac T, Flaherty L, Zha Y, Othus M, Ribas A, Sondak V, Gajewski T, et al. Phase 2 study of RO4929097, a gamma-secretase inhibitor, in metastatic melanoma: SWOG 0933. Cancer 2015; 121:432-40; PMID:25250858; http://dx.doi.org/10.1002/cncr.29055
  • De Jesus-Acosta A, Laheru D, Maitra A, Arcaroli J, Rudek M, Dasari A, Blatchford P, Quackenbush K, Messersmith W. A phase II study of the gamma secretase inhibitor RO4929097 in patients with previously treated metastatic pancreatic adenocarcinoma. Invest New Drug 2014; 32:739-45; PMID:24668033; http://dx.doi.org/10.1007/s10637-014-0083-8
  • Strosberg J, Yeatman T, Weber J, Coppola D, Schell M, Han G, Almhanna K, Kim R, Valone T, Jump H, et al. A phase II study of RO4929097 in metastatic colorectal cancer. Eur J Cancer 2012; 48:997-1003; PMID:22445247; http://dx.doi.org/10.1016/j.ejca.2012.02.056
  • Richter S, Bedard P, Chen E, Clarke B, Tran B, Hotte S, Stathis A, Hirte H, Razak A, Reedijk M, et al. A phase I study of the oral gamma secretase inhibitor R04929097 in combination with gemcitabine in patients with advanced solid tumors (PHL-078/CTEP 8575). Invest New Drugs 2014; 32:243-9; PMID:23645447; http://dx.doi.org/10.1007/s10637-013-9965-4
  • Dantas-Barbosa C, Bergthold G, Daudigeos-Dubus E, Blockus H, Boylan J, Ferreira C, Puget S, Abely M, Vassal G, Grill J, et al. Inhibition of the NOTCH pathway using γ-secretase inhibitor RO4929097 has limited antitumor activity in established glial tumors. Anticancer Drugs 2015; 26:272-83; PMID:25486598; http://dx.doi.org/10.1097/CAD.0000000000000190
  • van Stralen E, van de Wetering M, Agnelli L, Neri A, Clevers H, Bast B. Identification of primary MAFB target genes in multiple myeloma. Exp Hematol 2009; 37:78-86; PMID:19013005; http://dx.doi.org/10.1016/j.exphem.2008.08.006
  • Houde C, Li Y, Song L, Barton K, Zhang Q, Godwin J, Nand S, Toor A, Alkan S, Smadja NV, et al. Overexpression of the NOTCH ligand JAG2 in malignant plasma cells from multiple myeloma patients and cell lines. Blood 2004; 104:3697-704; PMID:15292061; http://dx.doi.org/10.1182/blood-2003-12-4114
  • Xu D, Hu J, De Bruyne E, Menu E, Schots R, Vanderkerken K, Van Valckenborgh E. Dll1/Notch activation contributes to bortezomib resistance by upregulating CYP1A1 in multiple myeloma. Biochem Biophys Res Commun 2012; 428:518-24; PMID:23111325; http://dx.doi.org/10.1016/j.bbrc.2012.10.071
  • Ding Y, Shen Y. Notch increased vitronection adhesion protects myeloma cells from drug induced apoptosis. Biochem Biophys Res Commun 2015; 467:717-22; PMID:26494298; http://dx.doi.org/10.1016/j.bbrc.2015.10.076
  • Mirandola L, Apicella L, Colombo M, Yu Y, Berta D, Platonova N, Lazzari E, Lancellotti M, Bulfamante G, Cobos E, et al. Anti-Notch treatment prevents multiple myeloma cells localization to the bone marrow via the chemokine system CXCR4/SDF-1. Leukemia 2013; 27:1558-66; PMID:23354012; http://dx.doi.org/10.1038/leu.2013.27
  • Colombo M, Thümmler K, Mirandola L, Garavelli S, Todoerti K, Apicella L, Lazzari E, Lancellotti M, Platonova N, Akbar M, et al. Notch signaling drives multiple myeloma induced osteoclastogenesis. Oncotarget 2014; 5:10393-406; PMID:25257302; http://dx.doi.org/10.18632/oncotarget.2084
  • Schwarzer R, Nickel N, Godau J, Willie B, Duda G, Schwarzer R, Cirovic B, Leutz A, Manz R, Bogen B, et al. Notch pathway inhibition controls myeloma bone disease in the murine MOPC315. BM model. Blood Cancer J 2014; 4:e217; PMID:24927406; http://dx.doi.org/10.1038/bcj.2014.37
  • He W, Luistro L, Carvajal D, Smith M, Nevins T, Yin X, Cai J, Higgins B, Kolinsky K, Rizzo C, et al. High tumor levels of IL6 and IL8 abrogate preclinical efficacy of the γ-secretase inhibitor, RO4929097. Mol Oncol 2011; 5:292-301; PMID:21315665; http://dx.doi.org/10.1016/j.molonc.2011.01.001
  • Chen F, Pisklakova A, Li M, Baz R, Sullivan D, Nefedova Y. Gamma-secretase inhibitor enhances the cytotoxic effect of bortezomib in multiple myeloma. Cell Oncol 2011; 34:545-51; PMID:21965140; http://dx.doi.org/10.1007/s13402-011-0060-6
  • Nefedova Y, Sullivan D, Bolick S, Dalton W, Gabrilovich D. Inhibition of Notch signaling induces apoptosis of myeloma cells and enhances sensitivity to chemotherapy. Blood 2008; 111:2220-9; PMID:18039953; http://dx.doi.org/10.1182/blood-2007-07-102632
  • Jakob C, Sterz J, Zavrski I, Heider U, Kleeberg L, Fleissner C, Kaiser M, Sezer O. Angiogenesis in multiple myeloma. Euro J Cancer 2006; 42:1581-90; PMID:16797965; http://dx.doi.org/10.1016/j.ejca.2006.02.017
  • Vacca A, Ribatti D. Bone marrow angiogenesis in multiple myeloma. Leukemia 2006; 20:193-9; PMID:16357836; http://dx.doi.org/10.1038/sj.leu.2404067
  • Ashley J, Ahn J, Hankenson K. Notch signaling promotes osteoclast maturation and resorptive activity. J Cell Biochem 2015; 116:2598-609; PMID:25914241; http://dx.doi.org/10.1002/jbc.25205
  • Kaiser M, Mieth M, Liebisch P, Oberländer R, Rademacher J, Jakob C, Kleeberg L, Fleissner C, Braendle E, Peters M, et al. Serum concentrations of DKK-1 correlate with the extent of bone disease in patients with multiple myeloma. Eur J Haematol 2008; 80:490-4; PMID:18331598; http://dx.doi.org/10.1111/j.1600-0609.2008.01065.x
  • Curry C, Reed L, Nickoloff B, Miele L, Foreman K. Notch-independent regulation of Hes-1 expression by c-Jun N-terminal kinase signaling in human endothelial cells. Lab Invest 2006; 86:842-52; PMID:16732296; http://dx.doi.org/10.1038/labinvest.3700442
  • Doetzlhofer A, Basch M, Ohyama T, Gessler M, Groves A, Segil N. Hey2 regulation by FGF provides a Notch-independent mechanism for maintaining pillar cell fate in the organ of Corti. Dev Cell 2009; 16:58-69; PMID:19154718; http://dx.doi.org/10.1016/j.devcel.2008.11.008
  • Nakazaki H, Reddy A, Mania-Farnell B, Shen Y, Ichi S, McCabe C, George D, McLone D, Tomita T, Mayanil C. Key basic helix-loop-helix transcription factor genes Hes1 and Ngn2 are regulated by Pax3 during mouse embryonic development. Dev Biol 2008; 316:510-23; PMID:18308300; http://dx.doi.org/10.1016/j.ydbio.2008.01.008
  • Jurczyszyn A, Czepiel J, Biesiada G, Gdula-Argasińska J, Cibor D, Owczarek D, Perucki W, Skotnicki A. HGF, sIL-6R and TGF-β1 play a significant role in the progression of multiple myeloma. J Cancer 2014; 5:518-24; PMID:24963356; http://dx.doi.org/10.7150/jca.9266
  • Urashima M, Ogata A, Chauhan D, Hatziyanni M, Vidriales M, Dedera D, Schlossman R, Anderson KC. Transforming growth factor-beta1: differential effects on multiple myeloma versus normal B cells. Blood 1996; 87:1928-38; PMID:8634441
  • Kurpinski K, Lam H, Chu J, Wang A, Kim A, Tsay E, Agrawal S, Schaffer D, Li S. Transforming growth factor-beta and notch signaling mediate stem cell differentiation into smooth muscle cells. Stem Cells 2010; 28:734-42; PMID:20146266; http://dx.doi.org/10.1002/stem.319
  • Kennard S, Liu H, Lilly B. Transforming growth factor-beta (TGF- 1) down-regulates Notch3 in fibroblasts to promote smooth muscle gene expression. J Biol Chem 2008; 283:1324-33; PMID:17981798; http://dx.doi.org/10.1074/jbc.M706651200
  • Blokzijl A, Dahlqvist C, Reissmann E, Falk A, Moliner A, Lendahl U, Ibáñez C. Cross-talk between the Notch and TGF-beta signaling pathways mediated by interaction of the Notch intracellular domain with Smad3. J Cell Biol 2003; 163:723-8; PMID:14638857; http://dx.doi.org/10.1083/jcb.200305112
  • Nyhan K, Faherty N, Murray G, Cooey L, Godson C, Crean J, Brazil D. Jagged/Notch signalling is required for a subset of TGFβ1 responses in human kidney epithelial cells. Biochim Biophys Acta 2010; 1803:1386-95; PMID:20833210; http://dx.doi.org/10.1016/j.bbamcr.2010.09.001
  • Samon J, Champhekar A, Minter L, Telfer J, Miele L, Fauq A, Das P, Golde T, Osborne B. Notch1 and TGFbeta1 cooperatively regulate Foxp3 expression and the maintenance of peripheral regulatory T cells. Blood 2008; 112:1813-21; PMID:18550850; http://dx.doi.org/10.1182/blood-2008-03-144980
  • Zhang Z, Wang H, Ikeda S, Fahey F, Bielenberg D, Smits P, Hauschka P. Notch3 in human breast cancer cell lines regulates osteoblast-cancer cell interactions and osteolytic bone metastasis. Am J Pathol 2010; 177:1459-69; PMID:20651241; http://dx.doi.org/10.2353/ajpath.2010.090476
  • Timmerman L, Grego-Bessa J, Raya A, Bertrán E, Pérez-Pomares J, Díez J, Aranda S, Palomo S, McCormick F, Izpisúa-Belmonte J, et al. Notch promotes epithelial-mesenchymal transition during cardiac development and oncogenic transformation. Genes Dev 2004; 18:99-115
  • Weidner N, Folkman J, Pozza F, Bevilacqua P, Allred E, Moore D, Meli S, Gasparini G. Tumor angiogenesis: a new significant and independent prognostic indicator in early-stage breast carcinoma. J Natl Cancer Inst 1992; 84:1875-87; PMID:1281237; http://dx.doi.org/10.1093/jnci/84.24.1875
  • Kerbel R. Tumor angiogenesis: past, present and the near future. Carcinogenesis 2000; 21:505-15; PMID:10688871; http://dx.doi.org/10.1093/carcin/21.3.505
  • Bertolini F, Mancuso P, Gobbi A, Pruneri G. The thin red line: angiogenesis in normal and malignant hematopoiesis. Exp Hematol 2000; 28:993-1000; PMID:11008011; http://dx.doi.org/10.1016/S0301-472X(00)00508-7
  • Rajkumar S, Mesa R, Fonseca R, Schroeder G, Plevak M, Dispenzieri A, Lacy M, Lust J, Witzig T, Gertz M, et al. Bone marrow angiogenesis in 400 patients with monoclonal gammopathy of undetermined significance, multiple myeloma, and primary amyloidosis. Clin Cancer Res 2002; 8:2210-6; PMID:12114422
  • Pruneri G, Ponzoni M, Ferreri A, Decarli N, Tresoldi M, Raggi F, Baldessari C, Freschi M, Baldini L, Goldaniga M, et al. Microvessel density, a surrogate marker of angiogenesis, is significantly related to survival in multiple myeloma patients. Br J Haematol 2002; 118:817-20; PMID:12181051; http://dx.doi.org/10.1046/j.1365-2141.2002.03654.x
  • Alexandrakis M, Pappa C, Kokonozaki M, Boula A, Vyzoukaki R, Staphylaki D, Papadopoulou A, Androulakis N, Tsirakis G, Sfiridaki A. Circulating serum levels of IL-20 in multiple myeloma patients: its significance in angiogenesis and disease activity. Med Oncol 2015; 32:42; PMID:25631632; http://dx.doi.org/10.1007/s12032-015-0488-z
  • Kangsamaksin T, Tattersall I, Kitajewski J. Notch functions in developmental and tumour angiogenesis by diverse mechanisms. Biochem Soc Trans 2014; 42:1563-8; PMID:25399571; http://dx.doi.org/10.1042/BST20140233
  • Bai S, Kopan R, Zou W, Hilton M, Ong C, Long F, Ross F, Teitelbaum S. NOTCH1 regulates osteoclastogenesis directly in osteoclast precursors and indirectly via osteoblast lineage cells. J Biol Chem 2008; 283:6509-18; PMID:18156632; http://dx.doi.org/10.1074/jbc.M707000200
  • Ashley J, Ahn J, Hankenson K. Notch signaling promotes osteoclast maturation and resorptive activity. J Cell Biochem 2015; 116:2598-609; PMID:25914241; http://dx.doi.org/10.1002/jcb.25205
  • Yamada T, Yamazaki H, Yamane T, Yoshino M, Okuyama H, Tsuneto M, Kurino T, Hayashi S, Sakano S. Regulation of osteoclast development by Notch signaling directed to osteoclast precursors and through stromal cells. Blood 2003; 101:2227-34; PMID:12411305; http://dx.doi.org/10.1182/blood-2002-06-1740
  • Tian E, Zhan F, Walker R, Rasmussen E, Ma Y, Barlogie B, Shaughnessy JJ. The role of the Wnt-signaling antagonist DKK1 in the development of osteolytic lesions in multiple myeloma. N Engl J Med 2003; 349:2483-94; PMID:14695408; http://dx.doi.org/10.1056/NEJMoa030847
  • Yang G, Xu Y, Chen H, Wang X. Acute lymphoblastic leukemia cells inhibit the differentiation of bone mesenchymal stem cells into osteoblasts in vitro by activating notch signaling. Stem Cells Int 2015; 2015:162410; PMID:26339248; http://dx.doi.org/10.1155/2015/162410

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.