Experimental Hematology
Volume 38, Issue 10 , Pages 860-867 , October 2010

The cytokine/chemokine pattern in the bone marrow environment of multiple myeloma patients

  • Yanran Cao

      Affiliations

    • Department of Internal Medicine II (Oncology/Hematology/Stem Cell Transplantation), University Cancer Center Hamburg (Hubertus Wald Tumorzentrum), University Medical Center Hamburg-Eppendorf, Hamburg, Germany
    • Corresponding Author InformationOffprint requests to: Yanran Cao, M.D., Center of Oncology, Department of Internal Medicine II, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany
    • ,
  • Tim Luetkens

      Affiliations

    • Department of Internal Medicine II (Oncology/Hematology/Stem Cell Transplantation), University Cancer Center Hamburg (Hubertus Wald Tumorzentrum), University Medical Center Hamburg-Eppendorf, Hamburg, Germany
    • ,
  • Sebastian Kobold

      Affiliations

    • Department of Internal Medicine II (Oncology/Hematology/Stem Cell Transplantation), University Cancer Center Hamburg (Hubertus Wald Tumorzentrum), University Medical Center Hamburg-Eppendorf, Hamburg, Germany
    • ,
  • York Hildebrandt

      Affiliations

    • Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
    • ,
  • Maja Gordic

      Affiliations

    • Department of Internal Medicine II (Oncology/Hematology/Stem Cell Transplantation), University Cancer Center Hamburg (Hubertus Wald Tumorzentrum), University Medical Center Hamburg-Eppendorf, Hamburg, Germany
    • ,
  • Nesrine Lajmi

      Affiliations

    • Department of Internal Medicine II (Oncology/Hematology/Stem Cell Transplantation), University Cancer Center Hamburg (Hubertus Wald Tumorzentrum), University Medical Center Hamburg-Eppendorf, Hamburg, Germany
    • ,
  • Sabrina Meyer

      Affiliations

    • Department of Internal Medicine II (Oncology/Hematology/Stem Cell Transplantation), University Cancer Center Hamburg (Hubertus Wald Tumorzentrum), University Medical Center Hamburg-Eppendorf, Hamburg, Germany
    • ,
  • Katrin Bartels

      Affiliations

    • Department of Internal Medicine II (Oncology/Hematology/Stem Cell Transplantation), University Cancer Center Hamburg (Hubertus Wald Tumorzentrum), University Medical Center Hamburg-Eppendorf, Hamburg, Germany
    • ,
  • Axel R. Zander

      Affiliations

    • Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
    • ,
  • Carsten Bokemeyer

      Affiliations

    • Department of Internal Medicine II (Oncology/Hematology/Stem Cell Transplantation), University Cancer Center Hamburg (Hubertus Wald Tumorzentrum), University Medical Center Hamburg-Eppendorf, Hamburg, Germany
    • ,
  • Nicolaus Kröger

      Affiliations

    • Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
    • ,
  • Djordje Atanackovic

      Affiliations

    • Department of Internal Medicine II (Oncology/Hematology/Stem Cell Transplantation), University Cancer Center Hamburg (Hubertus Wald Tumorzentrum), University Medical Center Hamburg-Eppendorf, Hamburg, Germany

Received 9 April 2010 ,Revised 10 June 2010 ,Accepted 21 June 2010.

References 

  1. Dispenzieri A, Lacy MQ, Greipp PR. Multiple myeloma. In:  Greer JP,  Foerster J,  Lukens JN,  Rodgers GM,  Paraskevas F,  Glader B editor. Wintrobe’s Clinical Hematology. 11th ed. Philadelphia: Lippincott Williams & Wilkins; 2004;p. 2583–2636
  2. Aggarwal R, Ghobrial IM, Roodman GD. Chemokines in multiple myeloma. Exp Hematol. 2006;34:1289–1295
  3. Kyle RA, Rajkumar SV. Multiple myeloma. N Engl J Med. 2004;351:1860–1873
  4. Higman MA, Vogelsang GB. Chronic graft versus host disease. Br J Haematol. 2004;125:435–454
  5. Barrett AJ, Rezvani K, Solomon S, et al. New developments in allotransplant immunology. Hematology Am Soc Hematol Educ Program. 2003;350–371
  6. Sherer Y, Shoenfeld Y. Autoimmune diseases and autoimmunity post-bone marrow transplantation. Bone Marrow Transplant. 1998;22:873–881
  7. Wood KJ, Sakaguchi S. Regulatory T cells in transplantation tolerance. Nat Rev Immunol. 2003;3:199–210
  8. Zorn E. CD4+CD25+ regulatory T cells in human hematopoietic cell transplantation. Semin Cancer Biol. 2006;16:150–159
  9. Shindo T, Ishikawa T, Fukunaga A, Hori T, Uchiyama T. Growth and differentiation advantages of CD4+ OX40+ T cells from allogeneic hematopoietic stem cell transplantation recipients. Biol Blood Marrow Transplant. 2008;14:268–281
  10. O’Shea JJ, Ma A, Lipsky P. Cytokines and autoimmunity. Nat Rev Immunol. 2002;2:37–45
  11. Salomon B, Bluestone JA. Complexities of CD28/B7: CTLA-4 costimulatory pathways in autoimmunity and transplantation. Annu Rev Immunol. 2001;19:225–252
  12. Atanackovic D, Cao Y, Kim JW, et al. The local cytokine and chemokine milieu within malignant effusions. Tumour Biol. 2008;29:93–104
  13. Glucksberg H, Storb R, Fefer A, et al. Clinical manifestations of graft-versus-host disease in human recipients of marrow from HL-A-matched sibling donors. Transplantation. 1974;18:295–304
  14. Greipp PR, San Miguel J, Durie BG, et al. International staging system for multiple myeloma. J Clin Oncol. 2005;23:3412–3420
  15. Blade J, Samson D, Reece D, et al. Criteria for evaluating disease response and progression in patients with multiple myeloma treated by high-dose therapy and haemopoietic stem cell transplantation. Myeloma Subcommittee of the EBMT. European Group for Blood and Marrow Transplant. Br J Haematol. 1998;102:1115–1123
  16. Hallek M, Bergsagel PL, Anderson KC. Multiple myeloma: increasing evidence for a multistep transformation process. Blood. 1998;91:3–21
  17. Van Riet I. Homing mechanisms of myeloma cells. Pathol Biol (Paris). 1999;47:98–108
  18. Arendt BK, Velazquez-Dones A, Tschumper RC, et al. Interleukin 6 induces monocyte chemoattractant protein-1 expression in myeloma cells. Leukemia. 2002;16:2142–2147
  19. Biswas P, Delfanti F, Bernasconi S, et al. Interleukin-6 induces monocyte chemotactic protein-1 in peripheral blood mononuclear cells and in the U937 cell line. Blood. 1998;91:258–265
  20. Garrett IR, Durie BG, Nedwin GE, et al. Production of lymphotoxin, a bone-resorbing cytokine, by cultured human myeloma cells. N Engl J Med. 1987;317:526–532
  21. 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
  22. Kawano M, Hirano T, Matsuda T, et al. Autocrine generation and requirement of BSF-2/IL-6 for human multiple myelomas. Nature. 1988;332:83–85
  23. Kroning H, Tager M, Thiel U, et al. Overproduction of IL-7, IL-10 and TGF-beta 1 in multiple myeloma. Acta Haematol. 1997;98:116–118
  24. Lacy MQ, Donovan KA, Heimbach JK, Ahmann GJ, Lust JA. Comparison of interleukin-1 beta expression by in situ hybridization in monoclonal gammopathy of undetermined significance and multiple myeloma. Blood. 1999;93:300–305
  25. 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
  26. Pellegrino A, Antonaci F, Russo F, et al. CXCR3-binding chemokines in multiple myeloma. Cancer Lett. 2004;207:221–227
  27. Pellegrino A, Ria R, Di Pietro G, et al. Bone marrow endothelial cells in multiple myeloma secrete CXC-chemokines that mediate interactions with plasma cells. Br J Haematol. 2005;129:248–256
  28. Podar K, Tai YT, Davies FE, et al. Vascular endothelial growth factor triggers signaling cascades mediating multiple myeloma cell growth and migration. Blood. 2001;98:428–435
  29. Podar K, Tai YT, Lin BK, et al. Vascular endothelial growth factor-induced migration of multiple myeloma cells is associated with beta 1 integrin- and phosphatidylinositol 3-kinase-dependent PKC alpha activation. J Biol Chem. 2002;277:7875–7881
  30. Vacca A, Ribatti D, Roccaro AM, Ria R, Palermo L, Dammacco F. Bone marrow angiogenesis and plasma cell angiogenic and invasive potential in patients with active multiple myeloma. Acta Haematol. 2001;106:162–169
  31. Vande Broek I, Asosingh K, Vanderkerken K, Straetmans N, Van Camp B, Van Riet I. Chemokine receptor CCR2 is expressed by human multiple myeloma cells and mediates migration to bone marrow stromal cell-produced monocyte chemotactic proteins MCP-1, -2 and -3. Br J Cancer. 2003;88:855–862
  32. Zhong H, Han B, Tourkova IL, et al. Low-dose paclitaxel prior to intratumoral dendritic cell vaccine modulates intratumoral cytokine network and lung cancer growth. Clin Cancer Res. 2007;13:5455–5462
  33. Zlotnik A. Chemokines and cancer. Int J Cancer. 2006;119:2026–2029
  34. Ohshima K, Akaiwa M, Umeshita R, Suzumiya J, Izuhara K, Kikuchi M. Interleukin-13 and interleukin-13 receptor in Hodgkin’s disease: possible autocrine mechanism and involvement in fibrosis. Histopathology. 2001;38:368–375
  35. Ellis MJ, Jenkins S, Hanfelt J, et al. Insulin-like growth factors in human breast cancer. Breast Cancer Res Treat. 1998;52:175–184
  36. Shurin MR, Shurin GV, Lokshin A, et al. Intratumoral cytokines/chemokines/growth factors and tumor infiltrating dendritic cells: friends or enemies?. Cancer Metastasis Rev. 2006;25:333–356
  37. Gu ZJ, Costes V, Lu ZY, et al. Interleukin-10 is a growth factor for human myeloma cells by induction of an oncostatin M autocrine loop. Blood. 1996;88:3972–3986
  38. Zdzisinska B, Bojarska-Junak A, Dmoszynska A, Kandefer-Szerszen M. Abnormal cytokine production by bone marrow stromal cells of multiple myeloma patients in response to RPMI8226 myeloma cells. Arch Immunol Ther Exp (Warsz). 2008;56:207–221
  39. Niida S, Kaku M, Amano H, et al. Vascular endothelial growth factor can substitute for macrophage colony-stimulating factor in the support of osteoclastic bone resorption. J Exp Med. 1999;190:293–298
  40. Raman D, Baugher PJ, Thu YM, Richmond A. Role of chemokines in tumor growth. Cancer Lett. 2007;256:137–165
  41. Tanaka Y, Abe M, Hiasa M, et al. Myeloma cell-osteoclast interaction enhances angiogenesis together with bone resorption: a role for vascular endothelial cell growth factor and osteopontin. Clin Cancer Res. 2007;13:816–823
  42. Pellegrino A, Vacca A, Scavelli C, Dammacco F. [Chemokines and tumors]. Recent Prog Med. 2002;93:642–654
  43. Alexandrakis MG, Passam FH, Kyriakou DS, et al. Serum level of interleukin-16 in multiple myeloma patients and its relationship to disease activity. Am J Hematol. 2004;75:101–106
  44. Lauta VM. A review of the cytokine network in multiple myeloma: diagnostic, prognostic, and therapeutic implications. Cancer. 2003;97:2440–2452
  45. Rand TH, Cruikshank WW, Center DM, Weller PF. CD4-mediated stimulation of human eosinophils: lymphocyte chemoattractant factor and other CD4-binding ligands elicit eosinophil migration. J Exp Med. 1991;173:1521–1528
  46. Seidel C, Borset M, Turesson I, Abildgaard N, Sundan A, Waage A. Elevated serum concentrations of hepatocyte growth factor in patients with multiple myeloma. The Nordic Myeloma Study Group. Blood. 1998;91:806–812
  47. Borset M, Seidel C, Hjorth-Hansen H, Waage A, Sundan A. The role of hepatocyte growth factor and its receptor c-Met in multiple myeloma and other blood malignancies. Leuk Lymphoma. 1999;32:249–256
  48. Derksen PW, de Gorter DJ, Meijer HP, et al. The hepatocyte growth factor/Met pathway controls proliferation and apoptosis in multiple myeloma. Leukemia. 2003;17:764–774
  49. Hov H, Holt RU, Ro TB, et al. A selective c-met inhibitor blocks an autocrine hepatocyte growth factor growth loop in ANBL-6 cells and prevents migration and adhesion of myeloma cells. Clin Cancer Res. 2004;10:6686–6694
  50. Goede V, Brogelli L, Ziche M, Augustin HG. Induction of inflammatory angiogenesis by monocyte chemoattractant protein-1. Int J Cancer. 1999;82:765–770
  51. Center DM, Kornfeld H, Cruikshank WW. Interleukin 16 and its function as a CD4 ligand. Immunol Today. 1996;17:476–481
  52. Hauser AE, Debes GF, Arce S, et al. Chemotactic responsiveness toward ligands for CXCR3 and CXCR4 is regulated on plasma blasts during the time course of a memory immune response. J Immunol. 2002;169:1277–1282
  53. Moller C, Stromberg T, Juremalm M, Nilsson K, Nilsson G. Expression and function of chemokine receptors in human multiple myeloma. Leukemia. 2003;17:203–210
  54. Moser K, Muehlinghaus G, Manz R, et al. Long-lived plasma cells in immunity and immunopathology. Immunol Lett. 2006;103:83–85
  55. Giuliani N, Bonomini S, Romagnani P, et al. CXCR3 and its binding chemokines in myeloma cells: expression of isoforms and potential relationships with myeloma cell proliferation and survival. Haematologica. 2006;91:1489–1497
  56. In:  Von J,  Ferrara LM,  Cooke KR,  Deeg HJ editor. Graft-vs.-host disease. 3rd ed. New York, NY: Marcel Dekker; 2005;p. 143
  57. Daneshpouy M, Socie G, Lemann M, Rivet J, Gluckman E, Janin A. Activated eosinophils in upper gastrointestinal tract of patients with graft-versus-host disease. Blood. 2002;99:3033–3040

PII: S0301-472X(10)00268-7

doi: 10.1016/j.exphem.2010.06.012

Experimental Hematology
Volume 38, Issue 10 , Pages 860-867 , October 2010

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