Myeloma as a model for the process of metastasis: Implications for therapy

Blood

Volumn 120, Issue 1, 2012, Pages 20-30

  Ghobrial, Irene M ^a  

^a HARVARD MEDICAL SCHOOL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2 (5 CHLORO 2 FLUOROPHENYL) 4 (4 PYRIDINYLAMINO)PTERIDINE; BHQ880; CHEMOKINE RECEPTOR CXCR4; FIBRONECTIN; GELATINASE A; GELATINASE B; GRANULOCYTE COLONY STIMULATING FACTOR; HERMES ANTIGEN; INTERLEUKIN 11; INTERLEUKIN 6; L SELECTIN; LAMININ; LY2157299; M PROTEIN; MICRORNA; NOTCH RECEPTOR; OSTEOCLAST DIFFERENTIATION FACTOR; PADGEM PROTEIN; PLERIXAFOR; RAC PROTEIN; RHO FACTOR; SOMATOMEDIN B; SOMATOMEDIN C; STROMAL CELL DERIVED FACTOR 1; STROMAL CELL DERIVED FACTOR 1ALPHA; SYNDECAN 1; TRANSCRIPTION FACTOR SLUG; TRANSCRIPTION FACTOR SNAIL; TRANSCRIPTION FACTOR TWIST; TRANSFORMING GROWTH FACTOR BETA; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG; UNINDEXED DRUG; UVOMORULIN; VASCULOTROPIN;

ANGIOGENESIS; BIOLOGICAL MODEL; BONE MARROW; CELL ADHESION; CELL DIFFERENTIATION; CELL GROWTH; CELL HOMING; CELL INVASION; CELL MIGRATION; CELL MOTILITY; CELL PROLIFERATION; CELL SURVIVAL; CYTOKINE RELEASE; DISEASE COURSE; DISTANT METASTASIS; EPITHELIAL MESENCHYMAL TRANSITION; FOLLOW UP; HEMATOPOIETIC STEM CELL; HUMAN; IMMUNOSURVEILLANCE; METASTASIS; MICROMETASTASIS; MONOCLONAL IMMUNOGLOBULINEMIA; MULTIPLE MYELOMA; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; REVIEW; SHEAR STRESS; SIGNAL TRANSDUCTION; STEM CELL MOBILIZATION; STEM CELL NICHE; TUMOR GROWTH; TUMOR MICROENVIRONMENT;

EID: 84863581473     PISSN: 00064971     EISSN: 15280020     Source Type: Journal    
DOI: 10.1182/blood-2012-01-379024     Document Type: Review

References (154)

1. Kyle RA, Rajkumar SV. Multiple myeloma. Blood. 2008;111(6):2962-2972.
2. Rajkumar SV. Multiple myeloma: 2011 update on diagnosis, risk-stratification, and management. Am J Hematol. 2011;86(1):57-65.
3. Talmadge JE, Fidler IJ. AACR centennial series: the biology of cancer metastasis: historical perspective. Cancer Res. 2010;70(14):5649-5669.
4. Fidler IJ. The biology of cancer metastasis. Semin Cancer Biol. 2011;21(2):71.
5. Valastyan S, Weinberg RA. Tumor metastasis: molecular insights and evolving paradigms. Cell. 2011;147(2):275-292.
6. Fidler IJ. The pathogenesis of cancer metastasis: the 'seed and soil' hypothesis revisited. Nat Rev Cancer. 2003;3(6):453-458. (Pubitemid 37328849)
7. Laird DJ, von Andrian UH, Wagers AJ. Stem cell trafficking in tissue development, growth, and disease. Cell. 2008;132(4):612-630. (Pubitemid 351253693)
8. Scadden DT. Circadian rhythms: stem cells traffic in time. Nature. 2008;452(7186):416-417. (Pubitemid 351450831)
9. Anderson KC, Carrasco RD. Pathogenesis of myeloma. Annu Rev Pathol. 2011;6:249-274.
10. Kumar S, Fonseca R, Dispenzieri A, et al. Prognostic value of angiogenesis in solitary bone plasmacytoma. Blood. 2003;101(5):1715-1717. (Pubitemid 36237565)
11. Frassica DA, Frassica FJ, Schray MF, Sim FH, Kyle RA. Solitary plasmacytoma of bone: Mayo Clinic experience. Int J Radiat Oncol Biol Phys. 1989;16(1):43-48. (Pubitemid 19045333)
12. Kyle RA, Durie BG, Rajkumar SV, et al. Monoclonal gammopathy of undetermined significance (MGUS) and smoldering (asymptomatic) multiple myeloma: IMWG consensus perspectives risk factors for progression and guidelines for monitoring and management. Leukemia. 2010;24(6):1121-1127.
13. Kyle RA, Rajkumar SV. Monoclonal gammopathy of undetermined significance and smoldering multiple myeloma. Hematol Oncol Clin North Am. 2007;21(6):1093-1113. (Pubitemid 350051347)
14. Rajkumar SV, Lacy MQ, Kyle RA. Monoclonal gammopathy of undetermined significance and smoldering multiple myeloma. Blood Rev. 2007;21(5):255-265. (Pubitemid 47212600)
15. Kyle RA, Therneau TM, Rajkumar SV, et al. A long-term study of prognosis in monoclonal gammopathy of undetermined significance. N Engl J Med. 2002;346(8):564-569. (Pubitemid 34438817)
16. Landgren O, Kyle RA, Pfeiffer RM, et al. Monoclonal gammopathy of undetermined significance (MGUS) consistently precedes multiple myeloma: a prospective study. Blood. 2009;113(22):5412-5417.
17. Dimopoulos MA, Pouli A, Anagnostopoulos A, et al. Macrofocal multiple myeloma in young patients: a distinct entity with favorable prognosis. Leuk Lymphoma. 2006;47(8):1553-1556. (Pubitemid 44364020)
18. García-Sanz R, Orfao A, Gonzalez M, et al. Primary plasma cell leukemia: clinical, immunophenotypic, DNA ploidy, and cytogenetic characteristics. Blood. 1999;93(3):1032-1037. (Pubitemid 29067869)
19. Bladé J, Kyle RA. IgD monoclonal gammopathy with long-term follow-up. Br J Haematol. 1994;88(2):395-396. (Pubitemid 24318192)
20. Bladé J, Fernandez de Larrea C, Rosinol L, Cibeira MT, Jimenez R, Powles R. Soft-tissue plasmacytomas in multiple myeloma: incidence, mechanisms of extramedullary spread, and treatment approach. J Clin Oncol. 2011;29(28):3805-3812.
21. Bladé J, Kyle RA, Greipp PR. Presenting features and prognosis in 72 patients with multiple myeloma who were younger than 40 years. Br J Haematol. 1996;93(2):345-351. (Pubitemid 26148738)
22. Churg J, Gordon AJ. Multiple myeloma; lesions of the extra-osseous hematopoietic system. Am J Clin Pathol. 1950;20(10):934-945.
23. Scadden DT. The stem-cell niche as an entity of action. Nature. 2006;441(7097):1075-1079. (Pubitemid 43990719)
24. Schofield R. The relationship between the spleen colony-forming cell and the haemopoietic stem cell. Blood Cells Mol Dis. 1978;4:7-25. (Pubitemid 8376317)
25. Sipkins DA, Wei X, Wu JW, et al. In vivo imaging of specialized bone marrow endothelial microdomains for tumour engraftment. Nature. 2005;435(7044):969-973. (Pubitemid 40896324)
26. Yin T, Li L. The stem cell niches in bone. J Clin Invest. 2006;116(5):1195-1201.
27. Lo Celso C, Fleming HE, Wu JW, et al. Live-animal tracking of individual haematopoietic stem/progenitor cells in their niche. Nature. 2009;457(7225):92-96.
28. Runnels JM, Carlson AL, Pitsillides C, et al. Optical techniques for tracking multiple myeloma engraftment, growth, and response to therapy. J Biomed Opt. 2011;16(1):011006.
29. Shiozawa Y, Pedersen EA, Havens AM, et al. Human prostate cancer metastases target the hematopoietic stem cell niche to establish footholds in mouse bone marrow. J Clin Invest. 2011;121(4):1298-1312.
30. Roodman GD. Mechanisms of bone metastasis. N Engl J Med. 2004;350(16):1655-1664.
31. Smith MC, Luker KE, Garbow JR, et al. CXCR4 regulates growth of both primary and metastatic breast cancer. Cancer Res. 2004;64(23):8604-8612. (Pubitemid 39552073)
32. Karnoub AE, Weinberg RA. Chemokine networks and breast cancer metastasis. Breast Dis. 2006;26:75-85. (Pubitemid 46647416)
33. Callander NS, Roodman GD. Myeloma bone disease. Semin Hematol. 2001;38(3):276-285. (Pubitemid 32717665)
34. Bryden AA, Islam S, Freemont AJ, Shanks JH, George NJ, Clarke NW. Parathyroid hormone-related peptide: expression in prostate cancer bone metastases. Prostate Cancer Prostatic Dis. 2002;5(1):59-62. (Pubitemid 34257309)
35. Devys A, Lortholary A, Audran M. PTHrP and breast cancer. Bull Cancer. 2001;88(11):1075-1080. (Pubitemid 34020161)
36. Calvi LM, Adams GB, Weibrecht KW, et al. Osteoblastic cells regulate the haematopoietic stem cell niche. Nature. 2003;425(6960):841-846. (Pubitemid 37351468)
37. Chirgwin JM, Guise TA. Molecular mechanisms of tumor-bone interactions in osteolytic metastases. Crit Rev Eukaryot Gene Expr. 2000;10(2):159-178.
38. Valastyan S, Weinberg RA. Tumor metastasis: molecular insights and evolving paradigms. Cell. 2011;147(2):275-292.
39. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2000;100(1):57-70.
40. Polyak K, Weinberg RA. Transitions between epithelial and mesenchymal states: acquisition of malignant and stem cell traits. Nat Rev Cancer. 2009;9(4):265-273.
41. Kalluri R, Weinberg RA. The basics of epithelial-mesenchymal transition. J Clin Invest. 2009;119(6):1420-1428.
42. Mani SA, Guo W, Liao MJ, et al. The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell. 2008;133(4):704-715. (Pubitemid 351636299)
43. Yang J, Mani SA, Donaher JL, et al. Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis. Cell. 2004;117(7):927-939. (Pubitemid 38798858)
44. Onder TT, Gupta PB, Mani SA, Yang J, Lander ES, Weinberg RA. Loss of E-cadherin promotes metastasis via multiple downstream transcriptional pathways. Cancer Res. 2008;68(10):3645-3654.
45. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646-674.
46. Gregory PA, Bracken CP, Bert AG, Goodall GJ. MicroRNAs as regulators of epithelial-mesenchymal transition. Cell Cycle. 2008;7(20):3112-3118.
47. Korpal M, Kang Y. The emerging role of miR-200 family of microRNAs in epithelial-mesenchymal transition and cancer metastasis. RNA Biol. 2008;5(3):115-119.
48. Cates JM, Dupont WD, Barnes JW, et al. Markers of epithelial-mesenchymal transition and epithelial differentiation in sarcomatoid carcinoma: utility in the differential diagnosis with sarcoma. Appl Immunohistochem Mol Morphol. 2008;16(3):251-262. (Pubitemid 351589558)
49. Hill RP, Marie-Egyptienne DT, Hedley DW. Cancer stem cells, hypoxia and metastasis. Semin Radiat Oncol. 2009;19(2):106-111.
50. Yang MH, Wu KJ. TWIST activation by hypoxia inducible factor-1 (HIF-1): implications in metastasis and development. Cell Cycle. 2008;7(14):2090-2096.
51. Lu X, Kang Y. Hypoxia and hypoxia-inducible factors: master regulators of metastasis. Clin Cancer Res. 2010;16(24):5928-5935.
52. Papayannopoulou T, Scadden DT. Stem-cell ecology and stem cells in motion. Blood. 2008;111(8):3923-3930.
53. Kucia M, Reca R, Miekus K, et al. Trafficking of normal stem cells and metastasis of cancer stem cells involve similar mechanisms: pivotal role of the SDF-1-CXCR4 axis. Stem Cells. 2005;23(7):879-894. (Pubitemid 41170944)
54. Petit I, Szyper-Kravitz M, Nagler A, et al. G-CSF induces stem cell mobilization by decreasing bone marrow SDF-1 and up-regulating CXCR4. Nat Immunol. 2002;3(7):687-694. (Pubitemid 34752479)
55. Lapidot T. Mechanism of human stem cell migration and repopulation of NOD/SCID and B2mnull NOD/SCID mice: the role of SDF-1/CXCR4 interactions. Ann N Y Acad Sci. 2001;938:83-95. (Pubitemid 32620021)
56. Cipolleschi MG, Dello Sbarba P, Olivotto M. The role of hypoxia in the maintenance of hematopoietic stem cells. Blood. 1993;82(7):2031-2037. (Pubitemid 23293984)
57. Alsayed Y, Ngo H, Runnels J, et al. Mechanisms of regulation of CXCR4/SDF-1 (CXCL12)-dependent migration and homing in multiple myeloma. Blood. 2007;109(7):2708-2717. (Pubitemid 46482062)
58. Azab AK, Runnels JM, Pitsillides C, et al. CXCR4 inhibitor AMD3100 disrupts the interaction of multiple myeloma cells with the bone marrow micro-environment and enhances their sensitivity to therapy. Blood. 2009;113(18):4341-4351.
59. Azab AK, Azab F, Blotta S, et al. RhoA and Rac1 GTPases play major and differential roles in stromal cell-derived factor-1-induced cell adhesion and chemotaxis in multiple myeloma. Blood. 2009;114(3):619-629.
60. Azab AK, Hu J, Quang P, et al. Hypoxia promotes dissemination of multiple myeloma through acquisition of endothelial to mesenchymal transitionlike features [published online ahead of print March 6, 2012]. Blood. doi:10.1182/blood-2011-09-380410.
61. Martin SK, Diamond P, Gronthos S, Peet DJ, Zannettino AC. The emerging role of hypoxia, HIF-1 and HIF-2 in multiple myeloma. Leukemia. 2011;25(10):1533-1542.
62. Colla S, Storti P, Donofrio G, et al. Low bone marrow oxygen tension and hypoxia-inducible factor-1alpha overexpression characterize patients with multiple myeloma: role on the transcriptional and proangiogenic profiles of CD138(+) cells. Leukemia. 2010;24(11):1967-1970.
63. Podar K, Anderson KC. A therapeutic role for targeting c-Myc/Hif-1-dependent signaling pathways. Cell Cycle. 2010;9(9):1722-1728.
64. Colla S, Storti P, Donofrio G, et al. Low bone marrow oxygen tension and hypoxia-inducible factor-1alpha overexpression characterize patients with multiple myeloma: role on the transcriptional and proangiogenic profiles of CD138(+) cells. Leukemia. 2010;24(11):1967-1970.
65. Douma S, Van Laar T, Zevenhoven J, Meuwissen R, Van Garderen E, Peeper DS. Suppression of anoikis and induction of metastasis by the neurotrophic receptor TrkB. Nature. 2004;430(7003):1034-1039.
66. Valentijn AJ, Zouq N, Gilmore AP. Anoikis. Biochem Soc Trans. 2004;32(3):421-425. (Pubitemid 38813528)
67. Konstantopoulos K, Thomas SN. Cancer cells in transit: the vascular interactions of tumor cells. Annu Rev Biomed Eng. 2009;11:177-202.
68. Nowakowski GS, Witzig TE, Dingli D, et al. Circulating plasma cells detected by flow cytometry as a predictor of survival in 302 patients with newly diagnosed multiple myeloma. Blood. 2005;106(7):2276-2279. (Pubitemid 41510796)
69. Kumar S, Rajkumar SV, Kyle RA, et al. Prognostic value of circulating plasma cells in monoclonal gammopathy of undetermined significance. J Clin Oncol. 2005;23(24):5668-5674.
70. Paiva B, Vidriales MB, Perez JJ, et al. The clinical utility and prognostic value of multiparameter flow cytometry immunophenotyping in light-chain amyloidosis. Blood. 2011;117(13):3613-3616.
71. Kyle RA, Rajkumar SV. Multiple myeloma. N Engl J Med. 2004;351(18):1860-1873.
72. Lapidot T, Dar A, Kollet O. How do stem cells find their way home? Blood. 2005;106(6):1901-1910. (Pubitemid 41291700)
73. Avecilla ST, Hattori K, Heissig B, et al. Chemokine-mediated interaction of hematopoietic progenitors with the bone marrow vascular niche is required for thrombopoiesis. Nat Med. 2004;10(1):64-71. (Pubitemid 38524700)
74. Kollet O, Shivtiel S, Chen YQ, et al. HGF, SDF-1, and MMP-9 are involved in stress-induced human CD34+ stem cell recruitment to the liver. J Clin Invest. 2003;112(2):160-169. (Pubitemid 38056352)
75. Peled A, Kollet O, Ponomaryov T, et al. The chemokine SDF-1 activates the integrins LFA-1, VLA-4, and VLA-5 on immature human CD34(+) cells: role in transendothelial/stromal migration and engraftment of NOD/SCID mice. Blood. 2000;95(11):3289-3296. (Pubitemid 30428455)
76. Peled A, Grabovsky V, Habler L, et al. The chemokine SDF-1 stimulates integrin-mediated arrest of CD34(+) cells on vascular endothelium under shear flow. J Clin Invest. 1999;104(9):1199-1211. (Pubitemid 29536291)
77. .Wysoczynski M, Reca R, Ratajczak J, et al. Incorporation of CXCR4 into membrane lipid rafts primes homing-related responses of hematopoietic stem/progenitor cells to an SDF-1 gradient. Blood. 2005;105(1):40-48. (Pubitemid 40053061)
78. Ding Z, Issekutz TB, Downey GP, Waddell TK. L-selectin stimulation enhances functional expression of surface CXCR4 in lymphocytes: implications for cellular activation during adhesion and migration. Blood. 2003;101(11):4245- 4252. (Pubitemid 36857784)
79. Fowler JA, Mundy GR, Lwin ST, Lynch CC, Edwards CM. A murine model of myeloma that allows genetic manipulation of the host microenvironment. Dis Model Mech. 2009;2(11):604-611.
80. Van Valckenborgh E, Mincher D, Di Salvo A, et al. Targeting an MMP-9-activated prodrug to multiple myeloma-diseased bone marrow: a proof of principle in the 5T33MM mouse model. Leukemia. 2005;19(9):1628-1633. (Pubitemid 43090408)
81. Podar K, Zimmerhackl A, Fulciniti M, et al. The selective adhesion molecule inhibitor Natalizumab decreases multiple myeloma cell growth in the bone marrow microenvironment: therapeutic implications. Br J Haematol. 2011;155(4):438-448.
82. Azab AK, Quang P, Azab F, et al. P-selectin glycoprotein ligand regulates the interaction of multiple myeloma cells with the bone marrow microenvironment. Blood. 2012;119(6):1468-1478.
83. Tai YT, Podar K, Catley L, et al. Insulin-like growth factor-1 induces adhesion and migration in human multiple myeloma cells via activation of beta1-integrin and phosphatidylinositol 3′-kinase/AKT signaling. Cancer Res. 2003;63(18):5850-5858. (Pubitemid 37187484)
84. Sanz-Rodríguez F, Hidalgo A, Teixido J. Chemokine stromal cell-derived factor-1alpha modulates VLA-4 integrin-mediated multiple myeloma cell adhesion to CS-1/fibronectin and VCAM-1. Blood. 2001;97(2):346-351. (Pubitemid 32060316)
85. Parmo-Cabañas M, Bartolome RA, Wright N, Hidalgo A, Drager AM, Teixido J. Integrin alpha4beta1 involvement in stromal cell-derived factor-1alpha-promoted myeloma cell transendothelial migration and adhesion: role of cAMP and the actin cytoskeleton in adhesion. Exp Cell Res. 2004;294(2):571-580. (Pubitemid 38326753)
86. Neri P, Ren L, Azab AK, et al. Integrin beta7-mediated regulation of multiple myeloma cell adhesion, migration, and invasion. Blood. 2011; 117(23):6202-6213.
87. Khotskaya YB, Dai Y, Ritchie JP, et al. Syndecan-1 is required for robust growth, vascularization, and metastasis of myeloma tumors in vivo. J Biol Chem. 2009;284(38):26085-26095.
88. Chen L, Sanderson RD. Heparanase regulates levels of syndecan-1 in the nucleus. PLoS One. 2009;4(3):e4947.
89. Mitsiades CS. CD44v6, a target for novel antibody treatment approaches, is frequently expressed in multiple myeloma and associated with deletion of chromosome arm 13q. Haematologica. 2005;90(4):436-437.
90. Vincent T, Mechti N. IL-6 regulates CD44 cell surface expression on human myeloma cells. Leukemia. 2004;18(5):967-975. (Pubitemid 38714622)
91. Psaila B, Lyden D. The metastatic niche: adapting the foreign soil. Nat Rev Cancer. 2009;9(4):285-293.
92. Psaila B, Kaplan RN, Port ER, Lyden D. Priming the 'soil' for breast cancer metastasis: the premetastatic niche. Breast Dis. 2006;26:65-74. (Pubitemid 46647415)
93. Kosaka N, Iguchi H, Yoshioka Y, Takeshita F, Matsuki Y, Ochiya T. Secretory mechanisms and intercellular transfer of microRNAs in living cells. J Biol Chem. 2010;285(23):17442-17452.
94. Kosaka N, Iguchi H, Ochiya T. Circulating micro- RNA in body fluid: a new potential biomarker for cancer diagnosis and prognosis. Cancer Sci. 2010;101(10):2087-2092.
95. Gao D, Nolan D, McDonnell K, et al. Bone marrow-derived endothelial progenitor cells contribute to the angiogenic switch in tumor growth and metastatic progression. Biochim Biophys Acta. 2009;1796(1):33-40.
96. Zhang H, Vakil V, Braunstein M, et al. Circulating endothelial progenitor cells in multiple myeloma: implications and significance. Blood. 2005;105(8):3286-3294.
97. Ergün S, Hohn HP, Kilic N, Singer BB, Tilki D. Endothelial and hematopoietic progenitor cells (EPCs and HPCs): hand in hand fate determining partners for cancer cells. Stem Cell Rev. 2008;4(3):169-177.
98. Yang M, Chen J, Su F, et al. Microvesicles secreted by macrophages shuttle invasion-potentiating micro-RNAs into breast cancer cells. Mol Cancer. 2011;10:117.
99. Rak J. Microparticles in cancer. Semin Thromb Hemost. 2010;36(8):888-906.
100. van Niel G, Porto-Carreiro I, Simoes S, Raposo G. Exosomes: a common pathway for a specialized function. J Biochem. 2006;140(1):13-21. (Pubitemid 44433541)
101. Pan BT, Johnstone RM. Fate of the transferrin receptor during maturation of sheep reticulocytes in vitro: selective externalization of the receptor. Cell. 1983;33(3):967-978.
102. Théry C, Regnault A, Garin J, et al. Molecular characterization of dendritic cell-derived exosomes: selective accumulation of the heat shock protein hsc73. J Cell Biol. 1999;147(3):599-610. (Pubitemid 29523465)
103. Raposo G, Nijman HW, Stoorvogel W, et al. B lymphocytes secrete antigen-presenting vesicles. J Exp Med. 1996;183(3):1161-1172. (Pubitemid 26113979)
104. Blanchard N, Lankar D, Faure F, et al. TCR activation of human T cells induces the production of exosomes bearing the TCR/CD3/zeta complex. J Immunol. 2002;168(7):3235-3241. (Pubitemid 34250383)
105. van Niel G, Raposo G, Candalh C, et al. Intestinal epithelial cells secrete exosome-like vesicles. Gastroenterology. 2001;121(2):337-349. (Pubitemid 32729381)
106. Mears R, Craven RA, Hanrahan S, et al. Proteomic analysis of melanoma-derived exosomes by two-dimensional polyacrylamide gel electrophoresis and mass spectrometry. Proteomics. 2004;4(12):4019-4031. (Pubitemid 39657475)
107. Raposo G, Tenza D, Mecheri S, Peronet R, Bonnerot C, Desaymard C. Accumulation of major histocompatibility complex class II molecules in mast cell secretory granules and their release upon degranulation. Mol Biol Cell. 1997;8(12):2631-2645. (Pubitemid 27528227)
108. Théry C, Ostrowski M, Segura E. Membrane vesicles as conveyors of immune responses. Nat Rev Immunol. 2009;9(8):581-593.
109. Giri PK, Schorey JS. Exosomes derived from M. Bovis BCG infected macrophages activate antigen-specific CD4+ and CD8+ T cells in vitro and in vivo. PLoS One. 2008;3(6):e2461.
110. Andreola G, Rivoltini L, Castelli C, et al. Induction of lymphocyte apoptosis by tumor cell secretion of FasL-bearing microvesicles. J Exp Med. 2002;195(10):1303-1316. (Pubitemid 34564332)
111. Kim JW, Wieckowski E, Taylor DD, Reichert TE, Watkins S, Whiteside TL. Fas ligand-positive membranous vesicles isolated from sera of patients with oral cancer induce apoptosis of activated T lymphocytes. Clin Cancer Res. 2005;11(3):1010-1020. (Pubitemid 40175748)
112. Liu C, Yu S, Zinn K, et al. Murine mammary carcinoma exosomes promote tumor growth by suppression of NK cell function. J Immunol. 2006;176(3):1375- 1385. (Pubitemid 43134279)
113. Clayton A, Mitchell JP, Court J, Linnane S, Mason MD, Tabi Z. Human tumor-derived exosomes down-modulate NKG2D expression. J Immunol. 2008;180(11):7249-7258.
114. Roccaro M, Sacco A, Azab AK, et al. Stroma-derived exosomes mediate oncogenesis in multiple myeloma [abstract]. Blood (ASH Annual Meeting Abstracts). 2011;118: Abstract 625.
115. Chambers AF, Groom AC, MacDonald IC. Dissemination and growth of cancer cells in metastatic sites. Nat Rev Cancer. 2002;2(8):563-572. (Pubitemid 37328923)
116. Kang Y, Siegel PM, Shu W, et al. A multigenic program mediating breast cancer metastasis to bone. Cancer Cell. 2003;3(6):537-549. (Pubitemid 36808649)
117. Nguyen DX, Bos PD, Massague J. Metastasis: from dissemination to organ-specific colonization. Nat Rev Cancer. 2009;9(4):274-284.
118. López-Anglada L, Gutierrez NC, Garcia JL, Mateos MV, Flores T, San Miguel JF. P53 deletion may drive the clinical evolution and treatment response in multiple myeloma. Eur J Haematol. 2010;84(4):359-361.
119. Bergsagel PL, Kuehl WM. Molecular pathogenesis and a consequent classification of multiple myeloma. J Clin Oncol. 2005;23(26):6333-6338. (Pubitemid 46218843)
120. Sheth N, Yeung J, Chang H. p53 nuclear accumulation is associated with extramedullary progression of multiple myeloma. Leuk Res. 2009;33(10):1357-1360.
121. Bhowmick NA, Chytil A, Plieth D, et al. TGF-beta signaling in fibroblasts modulates the oncogenic potential of adjacent epithelia. Science. 2004;303(5659):848-851. (Pubitemid 38174665)
122. .Walkley CR, Shea JM, Sims NA, Purton LE, Orkin SH. Rb regulates interactions between hematopoietic stem cells and their bone marrow microenvironment. Cell. 2007;129(6):1081-1095. (Pubitemid 46908695)
123. Raaijmakers MH, Mukherjee S, Guo S, et al. Bone progenitor dysfunction induces myelodysplasia and secondary leukaemia. Nature. 2010;464(7290):852-857.
124. Uchiyama H, Barut BA, Chauhan D, Cannistra SA, Anderson KC. Characterization of adhesion molecules on human myeloma cell lines. Blood. 1992;80(9):2306-2314.
125. Uchiyama H, Barut BA, Mohrbacher AF, Chauhan D, Anderson KC. Adhesion of human myeloma-derived cell lines to bone marrow stromal cells stimulates interleukin-6 secretion. Blood. 1993;82(12):3712-3720. (Pubitemid 24006055)
126. Damiano JS, Cress AE, Hazlehurst LA, Shtil AA, Dalton WS. Cell adhesion mediated drug resistance (CAM-DR): role of integrins and resistance to apoptosis in human myeloma cell lines. Blood. 1999;93(5):1658-1667. (Pubitemid 29102494)
127. Hazlehurst LA, Damiano JS, Buyuksal I, Pledger WJ, Dalton WS.Adhesion to fibronectin via beta1 integrins regulates p27kip1 levels and contributes to cell adhesion mediated drug resistance (CAM-DR). Oncogene. 2000;19(38):4319-4327.
128. Roodman GD. Role of the bone marrow micro-environment in multiple myeloma. J Bone Miner Res. 2002;17(11):1921-1925. (Pubitemid 35239190)
129. Podar K, Richardson PG, Hideshima T, Chauhan D, Anderson KC. The malignant clone and the bone-marrow environment. Best Pract Res Clin Haematol. 2007;20(4):597-612. (Pubitemid 350215375)
130. Podar K, Hideshima T, Chauhan D, Anderson KC. Targeting signalling pathways for the treatment of multiple myeloma. Expert Opin Ther Targets. 2005;9(2):359-381. (Pubitemid 40613874)
131. Podar K, Chauhan D, Anderson KC. Bone marrow microenvironment and the identification of new targets for myeloma therapy. Leukemia. 2009;23(1):10-24.
132. Yaccoby S, Pearse RN, Johnson CL, Barlogie B, Choi Y, Epstein J. Myeloma interacts with the bone marrow microenvironment to induce osteoclastogenesis and is dependent on osteoclast activity. Br J Haematol. 2002;116(2):278-290. (Pubitemid 34156975)
133. Vanderkerken K, De Leenheer E, Shipman C, et al. Recombinant osteoprotegerin decreases tumor burden and increases survival in a murine model of multiple myeloma. Cancer Res. 2003;63(2):287-289. (Pubitemid 36152481)
134. Komori T. Regulation of skeletal development by the Runx family of transcription factors. J Cell Biochem. 2005;95(3):445-453. (Pubitemid 41420175)
135. Komori T, Yagi H, Nomura S, et al. Targeted disruption of Cbfa1 results in a complete lack of bone formation owing to maturational arrest of osteoblasts. Cell. 1997;89(5):755-764. (Pubitemid 27516178)
136. Giuliani N, Colla S, Morandi F, et al. Myeloma cells block RUNX2/CBFA1 activity in human bone marrow osteoblast progenitors and inhibit osteoblast formation and differentiation. Blood. 2005;106(7):2472-2483. (Pubitemid 41510822)
137. Thirunavukkarasu K, Halladay DL, Miles RR, et al. The osteoblast-specific transcription factor Cbfa1 contributes to the expression of osteoprotegerin, a potent inhibitor of osteoclast differentiation and function. J Biol Chem. 2000;275(33):25163-25172.
138. Chauhan D, Singh AV, Brahmandam M, et al. Functional interaction of plasmacytoid dendritic cells with multiple myeloma cells: a therapeutic target. Cancer Cell. 2009;16(4):309-323.
139. Valastyan S, Weinberg RA. MicroRNAs: crucial multi-tasking components in the complex circuitry of tumor metastasis. Cell Cycle. 2009;8(21):3506-3512.
140. Valastyan S, Reinhardt F, Benaich N, et al. A pleiotropically acting microRNA, miR-31, inhibits breast cancer metastasis. Cell. 2009;137(6):1032- 1046.
141. Saad F. Src as a therapeutic target in men with prostate cancer and bone metastases. BJU Int. 2009;103(4):434-440.
142. Valastyan S, Weinberg RA. miR-31: a crucial overseer of tumor metastasis and other emerging roles. Cell Cycle. 2010;9(11):2124-2129.
143. Ebos JM, Lee CR, Cruz-Munoz W, Bjarnason GA, Christensen JG, Kerbel RS. Accelerated metastasis after short-term treatment with a potent inhibitor of tumor angiogenesis. Cancer Cell. 2009;15(3):232-239.
144. Pagnucco G, Cardinale G, Gervasi F. Targeting multiple myeloma cells and their bone marrow microenvironment. Ann N Y Acad Sci. 2004;1028:390-399. (Pubitemid 40361840)
145. Hideshima T, Chauhan D, Podar K, Schlossman RL, Richardson P, Anderson KC. Novel therapies targeting the myeloma cell and its bone marrow microenvironment. Semin Oncol. 2001;28(6):607-612. (Pubitemid 33134420)
146. Mukherjee S, Raje N, Schoonmaker JA, et al. Pharmacologic targeting of a stem/progenitor population in vivo is associated with enhanced bone regeneration in mice. J Clin Invest. 2008;118(2):491-504. (Pubitemid 351206540)
147. Hu J, Handisides DR, Van Valckenborgh E, et al. Targeting the multiple myeloma hypoxic niche with TH-302, a hypoxia-activated prodrug. Blood. 2010;116(9):1524-1527.
148. van de Donk NW, Kamps S, Mutis T, Lokhorst HM. Monoclonal antibody-based therapy as a new treatment strategy in multiple myeloma. Leukemia. 2012;26(2):199-213.
149. Boyd KD, Davies FE, Morgan GJ. Novel drugs in myeloma: harnessing tumour biology to treat myeloma. Recent Results Cancer Res. 2011;183:151-187.
150. Morgan GJ, Child JA, Gregory WM, et al. Effects of zoledronic acid versus clodronic acid on skeletal morbidity in patients with newly diagnosed multiple myeloma (MRC Myeloma IX): secondary outcomes from a randomised controlled trial. Lancet Oncol. 2011;12(8):743-752.
151. Body JJ, Facon T, Coleman RE, et al. A study of the biological receptor activator of nuclear factor-kappaB ligand inhibitor, denosumab, in patients with multiple myeloma or bone metastases from breast cancer. Clin Cancer Res. 2006;12(4):1221-1228. (Pubitemid 43342512)
152. Yaccoby S, Ling W, Zhan F, Walker R, Barlogie B, Shaughnessy JD Jr. Antibody-based inhibition of DKK1 suppresses tumor-induced bone resorption and multiple myeloma growth in vivo. Blood. 2007;109(5):2106-2111. (Pubitemid 46348212)
153. Mateos M, López-Corral L, Hernández M, et al. Smoldering multiple myeloma (SMM) at high-risk of progression to symptomatic disease: a phase III, randomized, multicenter trial based on lenalidomide-dexamethasone (Len-Dex) as induction therapy followed by maintenance therapy with Len alone vs no treatment [abstract]. Blood (ASH Annual Meeting Abstracts). 2011;118: Abstract 991.
154. Runnels JM, Carlson AL, Pitsillides C, et al. Optical techniques for tracking multiple myeloma engraftment, growth, and response to therapy. J Biomed Opt. 2011;16(1):011006.