| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Regular Articles |
Myeloma Institute for Research and Therapy, Arkansas Cancer Research Center, University of Arkansas for Medical Sciences, Little Rock, Arkansas
We have investigated the interaction between tumor cells and specific cells in their microenvironment using myeloma as a model. The role of myeloma-induced osteoclastogenesis in the disease was studied ex vivo. Myeloma plasma cells freshly purified from patients’ bone marrow attracted committed osteoclast (OC) precursors (n = 9; P < 0.01) and in 22 experiments directly induced their differentiation to multinucleated, bone-resorbing OCs (P < 0.00002) in a receptor activator of nuclear factor-
B ligand-mediated mechanism that was inhibited by the receptor activator of nuclear factor-B (RANK-Fc) in 13 experiments by 71 ± 12% (P < 0.008). In contrast, myeloma cells did not induce differentiation of peripheral blood mononuclear cells. Myeloma plasma cells cocultured with OCs retained their viability and proliferative activity for >13 weeks. After 14 days in coculture, the plasma cells from 29 patients had higher viability (P < 2 x 10-6), fewer apoptotic cells (P < 4 x 10-15), and a higher bromodeoxyuridine labeling index (P < 0.0006) than controls. Physical contact between OCs and myeloma cells was required for these effects to take place. No differences were observed between OCs from healthy donors and those from myeloma patients. Blocking interleukin 6 activity, while reducing survival of myeloma cells, had no effect on their proliferative activity. These results support data obtained from animal models and clinical observations on the essential role of the microenvironment in tumor sustenance and progression.
This article has been cited by other articles:
|
|
 |
|
  J. A. Fowler, G. R. Mundy, S. T. Lwin, C. C. Lynch, and C. M. Edwards A murine model of myeloma that allows genetic manipulation of the host microenvironment Dis. Model. Mech., November 1, 2009; 2(11-12): 604 - 611. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Zheng, Z. Cai, S. Wang, X. Zhang, J. Qian, S. Hong, H. Li, M. Wang, J. Yang, and Q. Yi Macrophages are an abundant component of myeloma microenvironment and protect myeloma cells from chemotherapy drug-induced apoptosis Blood, October 22, 2009; 114(17): 3625 - 3628. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Kukreja, S. Radfar, B.-H. Sun, K. Insogna, and M. V. Dhodapkar Dominant role of CD47-thrombospondin-1 interactions in myeloma-induced fusion of human dendritic cells: implications for bone disease Blood, October 15, 2009; 114(16): 3413 - 3421. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Pennisi, W. Ling, X. Li, S. Khan, J. D. Shaughnessy Jr, B. Barlogie, and S. Yaccoby The ephrinB2/EphB4 axis is dysregulated in osteoprogenitors from myeloma patients and its activation affects myeloma bone disease and tumor growth Blood, August 27, 2009; 114(9): 1803 - 1812. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Fulciniti, P. Tassone, T. Hideshima, S. Vallet, P. Nanjappa, S. A. Ettenberg, Z. Shen, N. Patel, Y.-t. Tai, D. Chauhan, et al. Anti-DKK1 mAb (BHQ880) as a potential therapeutic agent for multiple myeloma Blood, July 9, 2009; 114(2): 371 - 379. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-W. Qiang, B. Hu, Y. Chen, Y. Zhong, B. Shi, B. Barlogie, and J. D. Shaughnessy Jr Bortezomib induces osteoblast differentiation via Wnt-independent activation of {beta}-catenin/TCF signaling Blood, April 30, 2009; 113(18): 4319 - 4330. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Sezer Myeloma Bone Disease: Recent Advances in Biology, Diagnosis, and Treatment Oncologist, March 1, 2009; 14(3): 276 - 283. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
X. Li, A. Pennisi, and S. Yaccoby Role of decorin in the antimyeloma effects of osteoblasts Blood, July 1, 2008; 112(1): 159 - 168. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Geffroy-Luseau, G. Jego, R. Bataille, L. Campion, and C. Pellat-Deceunynck Osteoclasts support the survival of human plasma cells in vitro Int. Immunol., June 1, 2008; 20(6): 775 - 782. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Wang, L. Zhang, X. Han, J. Yang, J. Qian, S. Hong, P. Lin, Y. Shi, J. Romaguera, L. W. Kwak, et al. A Severe Combined Immunodeficient-hu In vivo Mouse Model of Human Primary Mantle Cell Lymphoma Clin. Cancer Res., April 1, 2008; 14(7): 2154 - 2160. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Mahtouk, D. Hose, J. De Vos, J. Moreaux, M. Jourdan, J. F. Rossi, T. Reme, H. Goldschmidt, and B. Klein Input of DNA Microarrays to Identify Novel Mechanisms in Multiple Myeloma Biology and Therapeutic Applications Clin. Cancer Res., December 15, 2007; 13(24): 7289 - 7295. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Neri, S. Kumar, M. T. Fulciniti, S. Vallet, S. Chhetri, S. Mukherjee, Y. Tai, D. Chauhan, P. Tassone, S. Venuta, et al. Neutralizing B-Cell Activating Factor Antibody Improves Survival and Inhibits Osteoclastogenesis in a Severe Combined Immunodeficient Human Multiple Myeloma Model Clin. Cancer Res., October 1, 2007; 13(19): 5903 - 5909. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Zhan, S. Colla, X. Wu, B. Chen, J. P. Stewart, W. M. Kuehl, B. Barlogie, and J. D. Shaughnessy Jr CKS1B, overexpressed in aggressive disease, regulates multiple myeloma growth and survival through SKP2- and p27Kip1-dependent and -independent mechanisms Blood, June 1, 2007; 109(11): 4995 - 5001. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. J. Bahlis, A. M. King, D. Kolonias, L. M. Carlson, H. Y. Liu, M. A. Hussein, H. R. Terebelo, G. E. Byrne Jr, B. L. Levine, L. H. Boise, et al. CD28-mediated regulation of multiple myeloma cell proliferation and survival Blood, June 1, 2007; 109(11): 5002 - 5010. [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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
Y. Tanaka, M. Abe, M. Hiasa, A. Oda, H. Amou, A. Nakano, K. Takeuchi, K. Kitazoe, S. Kido, D. Inoue, 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., February 1, 2007; 13(3): 816 - 823. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Chatterjee, S. Jain, T. Stuhmer, M. Andrulis, U. Ungethum, R.-J. Kuban, H. Lorentz, K. Bommert, M. Topp, D. Kramer, et al. STAT3 and MAPK signaling maintain overexpression of heat shock proteins 90{alpha} and {beta} in multiple myeloma cells, which critically contribute to tumor-cell survival Blood, January 15, 2007; 109(2): 720 - 728. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Kukreja, A. Hutchinson, K. Dhodapkar, A. Mazumder, D. Vesole, R. Angitapalli, S. Jagannath, and M. V. Dhodapkar Enhancement of clonogenicity of human multiple myeloma by dendritic cells J. Exp. Med., August 7, 2006; 203(8): 1859 - 1865. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Yaccoby The Phenotypic Plasticity of Myeloma Plasma Cells as Expressed by Dedifferentiation into an Immature, Resilient, and Apoptosis-Resistant Phenotype Clin. Cancer Res., November 1, 2005; 11(21): 7599 - 7606. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Oshima, M. Abe, J. Asano, T. Hara, K. Kitazoe, E. Sekimoto, Y. Tanaka, H. Shibata, T. Hashimoto, S. Ozaki, et al. Myeloma cells suppress bone formation by secreting a soluble Wnt inhibitor, sFRP-2 Blood, November 1, 2005; 106(9): 3160 - 3165. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Moreaux, F. W. Cremer, T. Reme, M. Raab, K. Mahtouk, P. Kaukel, V. Pantesco, J. De Vos, E. Jourdan, A. Jauch, et al. The level of TACI gene expression in myeloma cells is associated with a signature of microenvironment dependence versus a plasmablastic signature Blood, August 1, 2005; 106(3): 1021 - 1030. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Yin Chondroitin Synthase 1 Is a Key Molecule in Myeloma Cell-Osteoclast Interactions J. Biol. Chem., April 22, 2005; 280(16): 15666 - 15672. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Matsumoto and M. Abe The Importance of Notch Signaling in Myeloma Cell-Osteoclast Interactions IBMS BoneKEy, February 1, 2005; 2(2): 7 - 10. [Full Text] [PDF]
|
|
|
|
|
|
G. D. Roodman Osteoclasts and myeloma cells stick together Blood, October 15, 2004; 104(8): 2209 - 2209. [Full Text] [PDF]
|
|
|
|
|
|
M. Abe, K. Hiura, J. Wilde, A. Shioyasono, K. Moriyama, T. Hashimoto, S. Kido, T. Oshima, H. Shibata, S. Ozaki, et al. Osteoclasts enhance myeloma cell growth and survival via cell-cell contact: a vicious cycle between bone destruction and myeloma expansion Blood, October 15, 2004; 104(8): 2484 - 2491. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
