Stem Cells
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

First published online November 17, 2005
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
2005-0220v1
24/4/986    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Reprints/Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Gunn, W. G.
Right arrow Articles by Gregory, C. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Gunn, W. G.
Right arrow Articles by Gregory, C. A.
Submitted on May 16, 2005
Accepted on November 13, 2005

Original Article

A Crosstalk between Myeloma Cells and Marrow Stromal Cells Stimulates Production of DKK1 and IL-6: A Potential Role in the Development of Lytic Bone Disease and Tumor Progression in Multiple Myeloma

W. G. Gunn 1, A. Conley 1, L. Deininger 1, S. D. Olson 1, D. J. Prockop 1, C. A. Gregory 1*

1 Tulane University, New Orleans, Louisiana

* To whom correspondence should be addressed. E-mail: cgregory{at}tulane.edu.


  Abstract

Multiple myeloma (MM) is a malignancy of antibody-secreting plasma cells. B cell plasmacytomas stimulate bone resorption and angiogenesis, resulting in osteolytic lesions in the skeleton that persist upon successful treatment of the malignancy with chemotherapy. We found that an interaction between MM cells and mesenchymal stem cells (MSCs) from bone marrow stroma results in the formation and persistence of osteolytic bone lesions. It is known that MM cells activate osteoclast activity and secrete high levels of the Wnt inhibitor, Dickkopf-1, which prevents MSCs from differentiating into osteoblasts. We show that the Wnt signaling activator 6-bromoindirubin-3'-monoxime (BIO), releases MSCs from the osteoinhibitory effects of Dickkopf-1, whereas LiCl treatment does not. Additionally, we show that the >5 kDa fraction of MSCconditioned medium promotes the proliferation of Dickkopf-1-secreting MM cells, and that an IL6-neutralizing antibody blocks this effect. IL6 gene expression levels were higher in undifferentiated MSCs than in MSCs treated with osteogenic medium, remained high in the presence of Dkk1, and were reduced by BIO treatment. Therefore, BIO treatment reduces the MSC-stimulated proliferation of MM cells and may enable MSCs to repair existing osteolytic lesions.

Key Words. multiple myeloma, mesenchymal stem cell, osteolytic lesions, chemotherapy, Wnt signaling, 6-bromoindirubin-3'-monoxime, interleukin-6




This article has been cited by other articles:


Home page
 Proc. Natl. Acad. Sci. USAHome page
H. Ohtaki, J. H. Ylostalo, J. E. Foraker, A. P. Robinson, R. L. Reger, S. Shioda, and D. J. Prockop
Stem/progenitor cells from bone marrow decrease neuronal death in global ischemia by modulation of inflammatory/immune responses
PNAS, September 23, 2008; 105(38): 14638 - 14643.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
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]

Home page
 BloodHome page
Y.-W. Qiang, Y. Chen, O. Stephens, N. Brown, B. Chen, J. Epstein, B. Barlogie, and J. D. Shaughnessy Jr
Myeloma-derived Dickkopf-1 disrupts Wnt-regulated osteoprotegerin and RANKL production by osteoblasts: a potential mechanism underlying osteolytic bone lesions in multiple myeloma
Blood, July 1, 2008; 112(1): 196 - 207.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
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]

Home page
 Stem CellsHome page
G. Lazennec and C. Jorgensen
Concise Review: Adult Multipotent Stromal Cells and Cancer: Risk or Benefit?
Stem Cells, June 1, 2008; 26(6): 1387 - 1394.
[Abstract] [Full Text] [PDF]

Home page
 Stem CellsHome page
L. Raffaghello, G. Bianchi, M. Bertolotto, F. Montecucco, A. Busca, F. Dallegri, L. Ottonello, and V. Pistoia
Human Mesenchymal Stem Cells Inhibit Neutrophil Apoptosis: A Model for Neutrophil Preservation in the Bone Marrow Niche
Stem Cells, January 1, 2008; 26(1): 151 - 162.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
N. Giuliani, F. Morandi, S. Tagliaferri, M. Lazzaretti, G. Donofrio, S. Bonomini, R. Sala, M. Mangoni, and V. Rizzoli
Production of Wnt Inhibitors by Myeloma Cells: Potential Effects on Canonical Wnt Pathway in the Bone Microenvironment
Cancer Res., August 15, 2007; 67(16): 7665 - 7674.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
M. Magnusson, A. C. M. Brun, N. Miyake, J. Larsson, M. Ehinger, J. M. Bjornsson, A. Wutz, M. Sigvardsson, and S. Karlsson
HOXA10 is a critical regulator for hematopoietic stem cells and erythroid/megakaryocyte development
Blood, May 1, 2007; 109(9): 3687 - 3696.
[Abstract] [Full Text] [PDF]

Home page
 aacredbookHome page
J. D. Shaughnessy Jr.
Going Against the Grain: Promoting Wnt Signaling to Conquer Cancer
Am. Assoc. Cancer Res. Educ. Book, April 14, 2007; 2007(1): 19 - 24.
[Full Text] [PDF]

Home page
 BloodHome page
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]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
STEM CELLS THE ONCOLOGIST CME ALPHAMED PRESS JOURNALS
http://www.peprotech.com/
Copyright © 2005 by AlphaMed Press.