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Blood, 1 November 2005, Vol. 106, No. 9, pp. 3160-3165. Prepublished online as a Blood First Edition Paper on July 19, 2005; DOI 10.1182/blood-2004-12-4940. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-12-4940v1 106/9/3160    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Oshima, T. Articles by Matsumoto, T. Search for Related Content PubMed PubMed Citation Articles by Oshima, T. Articles by Matsumoto, T. Related Collections Neoplasia Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Myeloma cells suppress bone formation by secreting a soluble Wnt inhibitor, sFRP-2 Takashi Oshima, Masahiro Abe, Jin Asano, Tomoko Hara, Kenichi Kitazoe, Etsuko Sekimoto, Yoichi Tanaka, Hironobu Shibata, Toshihiro Hashimoto, Shuji Ozaki, Shinsuke Kido, Daisuke Inoue, and Toshio Matsumoto From the Department of Medicine and Bioregulatory Sciences, University of Tokushima Graduate School of Medicine, Tokushima, Japan. Multiple myeloma (MM) develops devastating bone destruction with enhanced bone resorption and suppressed bone formation. In contrast to enhanced osteoclastogenesis, little is known about the mechanism of impaired bone formation in MM. Because a canonical Wingless-type (Wnt) signaling pathway has recently been shown to play an important role in osteoblast differentiation, we examined whether MM cells affect a canonical Wnt pathway to suppress bone formation. Conditioned media from RPMI8226 and U266 MM cell lines and primary MM cells suppressed in vitro mineralization as well as alkaline phosphatase activity in osteoblasts induced by bone morphogenetic protein 2 (BMP-2). These cell lines constitutively produced a soluble Wnt inhibitor, secreted Frizzled-related protein 2 (sFRP-2), but not other Wnt inhibitors including sFRP-1, sFRP-3, and dickkopf 1 (DKK-1) at the protein level. Most MM cells from patients with advanced bone destructive lesions also expressed sFRP-2. Furthermore, exogenous sFRP-2 suppressed osteoblast differentiation induced by BMP-2, and immunodepletion of sFRP-2 significantly restored mineralized nodule formation in vitro, suggesting a predominant role for MM cell-derived sFRP-2 in the impairment of bone formation by MM. Thus, in addition to enhanced osteolysis, MM cells also suppress bone formation at least in part through an inhibition of the canonical Wnt pathway by secreting sFRP-2. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: Y.-W. Qiang, J. D. Shaughnessy Jr, and S. Yaccoby Wnt3a signaling within bone inhibits multiple myeloma bone disease and tumor growth Blood, July 15, 2008; 112(2): 374 - 382. [Abstract] [Full Text] [PDF] C. M. Edwards, J. R. Edwards, S. T. Lwin, J. Esparza, B. O. Oyajobi, B. McCluskey, S. Munoz, B. Grubbs, and G. R. 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Dimopoulos Myeloma bone disease and proteasome inhibition therapies Blood, August 15, 2007; 110(4): 1098 - 1104. [Abstract] [Full Text] [PDF] N. Giuliani, F. Morandi, S. Tagliaferri, M. Lazzaretti, S. Bonomini, M. Crugnola, C. Mancini, E. Martella, L. Ferrari, A. Tabilio, et al. The proteasome inhibitor bortezomib affects osteoblast differentiation in vitro and in vivo in multiple myeloma patients Blood, July 1, 2007; 110(1): 334 - 338. [Abstract] [Full Text] [PDF] S. Colla, F. Zhan, W. Xiong, X. Wu, H. Xu, O. Stephens, S. Yaccoby, J. Epstein, B. Barlogie, and J. D. Shaughnessy Jr The oxidative stress response regulates DKK1 expression through the JNK signaling cascade in multiple myeloma plasma cells Blood, May 15, 2007; 109(10): 4470 - 4477. [Abstract] [Full Text] [PDF] T. Hiraga, S. Kizaka-Kondoh, K. Hirota, M. Hiraoka, and T. Yoneda Hypoxia and Hypoxia-Inducible Factor-1 Expression Enhance Osteolytic Bone Metastases of Breast Cancer Cancer Res., May 1, 2007; 67(9): 4157 - 4163. [Abstract] [Full Text] [PDF] T. Standal, N. Abildgaard, U.-M. Fagerli, B. Stordal, O. Hjertner, M. Borset, and A. Sundan HGF inhibits BMP-induced osteoblastogenesis: possible implications for the bone disease of multiple myeloma Blood, April 1, 2007; 109(7): 3024 - 3030. [Abstract] [Full Text] [PDF] S. Yaccoby, W. Ling, F. Zhan, R. Walker, B. Barlogie, and J. D. Shaughnessy Jr Antibody-based inhibition of DKK1 suppresses tumor-induced bone resorption and multiple myeloma growth in vivo Blood, March 1, 2007; 109(5): 2106 - 2111. [Abstract] [Full Text] [PDF] N. Giuliani, V. Rizzoli, and G. D. Roodman Multiple myeloma bone disease: pathophysiology of osteoblast inhibition Blood, December 15, 2006; 108(13): 3992 - 3996. [Abstract] [Full Text] [PDF] A. D. Theocharis, C. Seidel, M. Borset, K. Dobra, V. Baykov, V. Labropoulou, I. Kanakis, E. Dalas, N. K. Karamanos, A. Sundan, et al. 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