Bone morphogenetic protein-4 inhibits proliferation and induces apoptosis of multiple myeloma cells
Tóm tắt
Bone morphogenetic proteins (BMPs) can be isolated from organic bone matrix and are able to initiate de novo cartilage and bone formation. Here it is shown that BMP-4 inhibited DNA synthesis in a dose-dependent manner in 3 IL-6–dependent multiple myeloma (MM) cell lines (OH-2, IH-1, and ANBL-6). In contrast, no effect on DNA synthesis was observed in 3 IL-6–independent MM cell lines (JJN-3, U266, and RPMI 8226). BMP-4 induced cell cycle growth arrest in the G0/G1 phase in OH-2 and ANBL-6 cells but not in IH-1 cells. BMP-4 induced apoptosis in OH-2 and IH-1 cells, but not significantly in ANBL-6 cells. Furthermore, BMP-4 induced apoptosis in freshly isolated MM cells from 4 of 13 patients. In the OH-2 and ANBL-6 cell lines and in a patient sample, immunoblotting showed that BMP-4 down-regulated IL-6–induced tyrosine phosphorylation of Stat3, suggesting a mechanism for the apparent antagonism between IL-6 and BMP-4. BMP-4 or analogues may be attractive therapeutic agents in MM because of possible beneficial effects on both tumor burden and bone disease.
Tài liệu tham khảo
Hallek, 1998, Multiple myeloma: increasing evidence for a multistep transformation process., Blood., 91, 3, 10.1182/blood.V91.1.3
Hawley, 1998, Growth control mechanisms in multiple myeloma., Leuk Lymphoma., 29, 465, 10.3109/10428199809050906
Portier, 1993, γ-Interferon in multiple myeloma: inhibition of interleukin-6 (IL- 6)-dependent myeloma cell growth and down-regulation of IL-6-receptor expression in vitro., Blood., 81, 3076, 10.1182/blood.V81.11.3076.3076
Jernberg-Wiklund, 1991, Recombinant interferon-γ inhibits the growth of IL-6–dependent human multiple myeloma cell lines in vitro., Eur J Haematol., 46, 231, 10.1111/j.1600-0609.1991.tb00546.x
Ludwig, 1998, Should α-interferon be included as standard treatment in multiple myeloma?, Eur J Cancer., 34, 12, 10.1016/S0959-8049(97)10046-6
Westin, 1995, Interferon alfa-2b versus no maintenance therapy during the plateau phase in multiple myeloma: a randomized study: Cooperative Study Group., Br J Haematol., 89, 561, 10.1111/j.1365-2141.1995.tb08364.x
Quesada, 1988, Recombinant interferon gamma in hairy cell leukemia, multiple myeloma, and Waldenstrom's macroglobulinemia., Am J Hematol., 29, 1, 10.1002/ajh.2830290102
Brosh, 1995, The plasmacytoma growth inhibitor restrictin-P is an antagonist of interleukin 6 and interleukin 11: identification as a stroma-derived activin A., J Biol Chem., 270, 29594, 10.1074/jbc.270.49.29594
Koseki, 1998, Correlation between Bcl-X expression and B-cell hybridoma apoptosis induced by activin A., Cell Signal., 10, 517, 10.1016/S0898-6568(97)00191-5
Nishihara, 1993, Activin A induces apoptotic cell death., Biochem Biophys Res Commun., 197, 985, 10.1006/bbrc.1993.2576
Yamato, 1997, Activin A induction of cell-cycle arrest involves modulation of cyclin D2 and p21CIP1/WAF1 in plasmacytic cells., Mol Endocrinol., 11, 1044, 10.1210/mend.11.8.9953
Börset, 1999, Apoptosis, proliferation and NF-kB activation induced by agonistic Fas antibodies in the human myeloma cell line OH-2: amplification of Fas-mediated apoptosis by tumor necrosis factor., Eur J Haematol., 63, 345, 10.1111/j.1600-0609.1999.tb01138.x
Gazitt, 1999, TRAIL is a potent inducer of apoptosis in myeloma cells derived from multiple myeloma patients and is not cytotoxic to hematopoietic stem cells., Leukemia., 13, 1817, 10.1038/sj.leu.2401501
Urist, 1965, Bone: formation by autoinduction., Science., 150, 893, 10.1126/science.150.3698.893
Reddi, 1972, Biochemical sequences in the transformation of normal fibroblasts in adolescent rats., Proc Natl Acad Sci U S A., 69, 1601, 10.1073/pnas.69.6.1601
Sakou, 1998, Bone morphogenetic proteins: from basic studies to clinical approaches., Bone., 22, 591, 10.1016/S8756-3282(98)00053-2
Sakou, 1999, Localization of Smads, the TGF-β family intracellular signaling components during endochondral ossification., J Bone Miner Res., 14, 1145, 10.1359/jbmr.1999.14.7.1145
Reddi, 1994, Bone and cartilage differentiation., Curr Opin Genet Dev., 4, 737, 10.1016/0959-437X(94)90141-O
Gori, 1999, Differentiation of human marrow stromal precursor cells: bone morphogenetic protein-2 increases OSF2/CBFA1, enhances osteoblast commitment, and inhibits late adipocyte maturation., J Bone Miner Res., 14, 1522, 10.1359/jbmr.1999.14.9.1522
Abe, 2000, Essential requirement of BMPs-2/4 for both osteoblast and osteoclast formation in murine bone marrow cultures from adult mice: antagonism by noggin., J Bone Miner Res., 15, 663, 10.1359/jbmr.2000.15.4.663
Linkhart, 1996, Growth factors for bone growth and repair: IGF, TGF beta and BMP., Bone., 19, 1S, 10.1016/S8756-3282(96)00138-X
Rodriguez-Leon, 1999, Retinoic acid regulates programmed cell death through BMP signalling., Nat Cell Biol., 1, 125, 10.1038/10098
Graham, 1994, The signalling molecule BMP4 mediates apoptosis in the rhombencephalic neural crest., Nature., 372, 684, 10.1038/372684a0
Schmidt, 1998, Experimental induction of BMP-4 expression leads to apoptosis in the paraxial and lateral plate mesoderm., Dev Biol., 202, 253, 10.1006/dbio.1998.9011
Ide, 1997, Growth regulation of human prostate cancer cells by bone morphogenetic protein-2., Cancer Res., 57, 5022
Soda, 1998, Antiproliferative effects of recombinant human bone morphogenetic protein-2 on human tumor colony-forming units., Anticancer Drugs., 9, 327, 10.1097/00001813-199804000-00006
Kleeff, 1999, Bone morphogenetic protein 2 exerts diverse effects on cell growth in vitro and is expressed in human pancreatic cancer in vivo., Gastroenterology., 116, 1202, 10.1016/S0016-5085(99)70024-7
Harris, 1994, Expression of bone morphogenetic protein messenger RNAs by normal rat and human prostate and prostate cancer cells., Prostate., 24, 204, 10.1002/pros.2990240406
Hamdy, 1997, Immunolocalization and messenger RNA expression of bone morphogenetic protein-6 in human benign and malignant prostatic tissue., Cancer Res., 57, 4427
Huber, 1998, Transcriptional regulation of blood formation during Xenopus development., Semin Immunol., 10, 103, 10.1006/smim.1998.0111
Kawai, 1994, Development of hemopoietic bone marrow within the ectopic bone induced by bone morphogenetic protein., Blood Cells., 20, 191
Detmer, 1999, Lineage-restricted expression of bone morphogenetic protein genes in human hematopoietic cell lines., Blood Cells Mol Dis., 25, 310, 10.1006/bcmd.1999.0259
Ploemacher, 1999, Bone morphogenetic protein 9 is a potent synergistic factor for murine hemopoietic progenitor cell generation and colony formation in serum- free cultures., Leukemia., 13, 428, 10.1038/sj.leu.2401363
Bhatia, 1999, Bone morphogenetic proteins regulate the developmental program of human hematopoietic stem cells., J Exp Med., 189, 1139, 10.1084/jem.189.7.1139
Börset, 1994, TNF and IL-6 are potent growth factors for OH-2, a novel human myeloma cell line., Eur J Haematol., 53, 31, 10.1111/j.1600-0609.1994.tb00176.x
Börset, 1993, Lack of IL-1 secretion from human myeloma cells highly purified by immunomagnetic separation., Br J Haematol., 85, 446, 10.1111/j.1365-2141.1993.tb03331.x
Catlett-Falcone, 1999, Constitutive activation of Stat3 signaling confers resistance to apoptosis in human U266 myeloma cells., Immunity., 10, 105, 10.1016/S1074-7613(00)80011-4
Ogata, 1997, IL-6 triggers cell growth via the Ras-dependent mitogen-activated protein kinase cascade., J Immunol., 159, 2212, 10.4049/jimmunol.159.5.2212
Darnell, 1997, STATs and gene regulation., Science., 277, 1630, 10.1126/science.277.5332.1630
Heldin, 1997, TGF-beta signalling from cell membrane to nucleus through SMAD proteins., Nature., 390, 465, 10.1038/37284
Derynck, 1998, Smads: transcriptional activators of TGF-beta responses., Cell., 95, 737, 10.1016/S0092-8674(00)81696-7
Kang, 1996, Roles of protein phosphatase 1 and 2A in an IL-6-mediated autocrine growth loop of human myeloma cells., Cell Immunol., 168, 174, 10.1006/cimm.1996.0064
Schwarze, 1995, Prevention of myeloma cell apoptosis by ectopic bcl-2 expression or interleukin 6-mediated up-regulation of bcl-xL., Cancer Res., 55, 2262
Egle, 1997, Expression of Apo-1/Fas (CD95), Bcl-2, Bax and Bcl-x in myeloma cell lines: relationship between responsiveness to anti-Fas mab and p53 functional status., Br J Haematol., 97, 418, 10.1046/j.1365-2141.1997.382680.x
Korsmeyer, 1992, Bcl-2 initiates a new category of oncogenes: regulators of cell death., Blood., 80, 879, 10.1182/blood.V80.4.879.879
Ishisaki, 1999, Differential inhibition of Smad6 and Smad7 on bone morphogenetic protein- and activin-mediated growth arrest and apoptosis in B cells., J Biol Chem., 274, 13637, 10.1074/jbc.274.19.13637
Iwasaki, 1999, Specific activation of the p38 mitogen-activated protein kinase signaling pathway and induction of neurite outgrowth in PC12 cells by bone morphogenetic protein-2., J Biol Chem., 274, 26503, 10.1074/jbc.274.37.26503
Gupta, 1999, Protein kinase A is a negative regulator of renal branching morphogenesis and modulates inhibitory and stimulatory bone morphogenetic proteins., J Biol Chem., 274, 26305, 10.1074/jbc.274.37.26305
Ogata, 1994, Inhibitory effect of all-trans retinoic acid on the growth of freshly isolated myeloma cells via interference with interleukin-6 signal transduction., Blood., 84, 3040, 10.1182/blood.V84.9.3040.3040
Chauhan, 1997, Interleukin-6 inhibits Fas-induced apoptosis and stress-activated protein kinase activation in multiple myeloma cells., Blood., 89, 227, 10.1182/blood.V89.1.227
Urashima, 1997, Interleukin-6 overcomes p21WAF1 up-regulation and G1 growth arrest induced by dexamethasone and interferon-γ in multiple myeloma cells., Blood., 90, 279, 10.1182/blood.V90.1.279
Spets, 1998, Fas/APO-1 (CD95)-mediated apoptosis is activated by interferon-gamma and interf., Blood., 92, 2914, 10.1182/blood.V92.8.2914
Hata, 1995, Expression of Fas/Apo-1 (CD95) and apoptosis in tumor cells from patients with plasma cell disorders., Blood., 86, 1939, 10.1182/blood.V86.5.1939.bloodjournal8651939
Lichtenstein, 1995, Interleukin-6 inhibits apoptosis of malignant plasma cells., Cell Immunol., 162, 248, 10.1006/cimm.1995.1076
Berger, 1997, Interferon-beta interrupts interleukin-6–dependent signaling events in myeloma cells., Blood., 89, 261, 10.1182/blood.V89.1.261
Westendorf, 1995, Expression and function of Fas (APO-1/CD95) in patient myeloma cells and myeloma cell lines., Blood., 85, 3566, 10.1182/blood.V85.12.3566.bloodjournal85123566
Weber, 1998, Evidence for the up-regulation of osteogenic protein-1 mRNA expression in musculoskeletal neoplasms., J Orthop Res., 16, 8, 10.1002/jor.1100160103
Clement, 1999, Expression of bone morphogenetic protein 6 in normal mammary tissue and breast cancer cell lines and its regulation by epidermal growth factor., Int J Cancer., 80, 250, 10.1002/(SICI)1097-0215(19990118)80:2<250::AID-IJC14>3.0.CO;2-D
Durie, 1975, A clinical staging system for multiple myeloma: correlation of measured myeloma cell mass with presenting clinical features, response to treatment, and survival., Cancer., 36, 842, 10.1002/1097-0142(197509)36:3<842::AID-CNCR2820360303>3.0.CO;2-U