Relationship between abnormal osteoblasts and cellular immunity in multiple myeloma

Cancer Cell International

Zonghong Shao¹  Linmin Xing¹  Huaquan Wang¹  Hui Liu¹  Jing Li¹  Fengping Peng¹  Shan Gao¹  Rong Fu¹ 

[1] Department of Hematology, General Hospital, Tianjin Medical University, 154 Anshan Street, Heping District, Tianjin 300052, China

关键词: Bortezomib;    Cellular immunity;    Osteoblast;    Multiple myeloma;   

Others  :  1121673
DOI  :  10.1186/1475-2867-14-62

 received in 2013-11-24, accepted in 2014-06-09,  发布年份 2014

【 摘 要 】

Bone destruction and abnormal immunity always occur in patients with multiple myeloma (MM), which manifested by impaired osteoblasts and immune system. In this study, we investigated the quantity and function of osteoblasts by co-culture, the status of cellular immunity by flow cytometry, and the relationship between them in MM patients. The results showed that the numbers and function of osteoblasts in MM patients were lower than those in normal controls. Bortezomib could increase the numbers, calcium depositions and the expression of Bone morphogenetic protein–2 (BMP-2) mRNA of osteoblasts from MM patients in vitro. The status of cellular immunity in MM patients was abnormal, including decreased ratio of CD4⁺/CD8⁺, DC1/DC2 and Th1/Th2, and increased ratio of regulatory T cells. The ratio of CD4⁺/CD8⁺(r = 0.685) and CD4⁺CD25⁺/CD3⁺T(r = 0.568) were positively correlated with the quantity of osteoblasts (both P < 0.05). The serum interleukin-7(IL-7) level of MM patients was higher than that of normal controls (2.07 ± 0.71 vs. 1.62 ± 0.15 ng/L, P < 0.05), and was negatively correlated with the quantity of osteoblasts (r = -0.682, P < 0.01). Our data indicated that the proliferation and osteogenic potential of osteoblasts in MM patients were decreased which could be recovered by bortezomib in vitro. The down-regulation of cellular immunity was correlated with the quantity of osteoblasts.

【 授权许可】

   
2014 Fu et al.; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Lentzsch S, Ehrlich LA, Roodman GD: Pathophysiology of multiple myeloma bone disease. Hematol Oncol Clin North Am 2007, 21:1035-1049.
• [2]Terpos E, Sezer O, Croucher P: Myeloma bone disease and proteasome inhibition therapies. Blood 2007, 110:1098-1104.
• [3]Noonan K, Borrello I: The immune microenvironment o f myeloma. Cancer Microenviron 2011, 4:313-323.
• [4]Lorenzo J, Horowitz M, Choi Y: Osteoimmunology: interactions of the bone and immune system. Endocr Rev 2008, 29:403-440.
• [5]Beloti MM, Rosa AL: Osteoblast differentiation of human BM cells under continuous and discontinuous treatment with dexamethasone. Braz Dent J 2005, 16:156-161.
• [6]Harbers GM, Healy KE: The effect of ligand type and density on osteoblast adhesion, proliferation, and matrix mineralization. J Biomed Mater Res A 2005, 75:855-869.
• [7]Pinzone JJ, Hall BM, Thudi NK: The role of dickkopf-1 in bone development, homeostasis, and disease. Blood 2009, 113:517-525.
• [8]Qiang YW, Shaughnessy JD Jr, Yaccoby S: Wnt3a signaling within bone inhibits multiple myeloma bone disease and tumor growth. Blood 2008, 15:374-382.
• [9]Medinger M, Fischer N, Tzankov A: Vascular endothelial growth factor-related pathways in hemato-lymphoid malignancies. J Oncol 2010, 729725. doi:10.1155/2012/753407
• [10]Danylesko I, Beider K: Avichai shimoni. Novel strategies for immunotherapy in multiple myeloma: previous experience and future directions. Clin Dev Immunol 2012, 2012:797165. doi:10.1155/2012/797165
• [11]Sakaguchi S: Regulatory T, cells: key controllers of immunologic selftolerance. Cell 2000, 101:455-458.
• [12]Brygida B, John C, Jeremy L, Jeffrey A: Bluestone and Kevan C. Herold. TCR stimulation with modified anti-CD3 mAb expands CD8 + T cell population and induces CD8 + CD25 + Tregs. J Clin Invest 2005, 115:2904-2913.
• [13]Li H, Hong S, Qian J: Cross talk between the bone and immune systems: osteoclasts function as antigen-presenting cells and activate CD4 and CD8 T cells. Blood 2010, 116:210-217.
• [14]Bikker A, Kruize AA, van der Wurff-Jacobs KM, Peters RP, Kleinjan M, Redegeld F, de Jager W, Lafeber FP, van Roon JA: Interleukin-7 and toll-like receptor 7 induce synergistic B cell and T cell activation. Plos One 2014, 9(4):e94756.
• [15]Castella B, Riganti C, Fiore F: Immune modulation by zoledronic acid in human myeloma: an advantageous cross-talk between Vγ9Vδ2 T cells, αβCD8 + T cells, regulatory T cells, and dendritic cells. J Immunol 2011, 187:1578-1590.
• [16]Roodman GD: Bone building with bortezomib. J Clin Invest 2008, 118:462-464.
• [17]Giuliani N, Morandi F, Tagliaferri S, Lazzaretti M, Bonomini S, Crugnola M, Mancini C, Martella E, Ferrari L, Tabilio A, Rizzoli V: The proteasome inhibitor bortezomib affects osteoblast differentiation in vitro and in vivo in multiple myeloma patients. Blood 2007, 110(1):334-338.
• [18]Mohty M, Malard F, Mohty B, Savani B, Moreau P, Terpos E: The effects of bortezomib on bone disease in patients with multiple myeloma. Cancer 2014, 120(5):618-623.