| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Tumor Biology |
B Ligand (RANKL) Is a Key Molecule of Osteoclast Formation for Bone Metastasis in a Newly Developed Model of Human Neuroblastoma1
Department of Environmental Medicine, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka 594-1101, Japan
Neuroblastoma originates from neural crest cells and is the most common
extracranial solid tumor in childhood. Bone metastasis in neuroblastoma
is an unfavorable prognostic factor even with intensive therapy. In the
present study, we screened four cell lines of human neuroblastoma
(NB-1, NB-16, NB-19, and NH-6) for tumorigenicity and metastatic
capacity in nude mice and found that NB-19 cells caused osteolytic
lesions after s.c. injection into mice. To detect micrometastases in
the host tissue, we performed two kinds of PCR-based metastasis assays:
(a) genomic PCR assay using the primers for human
genome-specific Alu sequence; and (b) reverse
transcription-nested PCR assay that detects the expression of tyrosine
hydroxylase, a marker specific for neuroblastoma. The results of these
PCR assays revealed the colonization of human neuroblastoma cells in
the bone marrow of the mice that had received the s.c. injection of
NB-19 cells. Because osteoclastic bone resorption has been reported to
play important roles in osteolysis in some cancers such as breast
cancer, we next examined the osteoclast (OC)-inducing activity of NB-19
cells using a coculture system in which NB-19 cells were cultured with
murine bone marrow cells containing OC precursors and stromal cells.
NB-19 cells induced tartrate-resistant acid phosphatase-positive
multinucleated OC-like cells without requirement of
1,25-dihydroxyvitamin D3 or other osteoclastogenic
stimulators. To investigate the factors involved in the
osteoclastogenesis in the coculture of mouse marrow cells and NB-19
cells, we performed reverse transcription-PCR analysis and revealed the
increased expression of receptor activator of nuclear factor 
B
ligand (RANKL) in the coculture compared with the culture of bone
marrow cells alone. Interleukin-1
and cyclooxygenase-2 expression in
the murine marrow cells was also increased in the presence of NB-19
cells. To further study the role of RANKL in the OC-like cell formation
in the coculture of NB-19 cells and murine marrow cells, an expression
vector encoding the active portion of the murine osteoprotegerin, which
is the native inhibitor of RANKL action, was constructed and introduced
into COS-7 cells. The conditioned media of the COS-7 cells transfected
with the osteoprotegerin expression vector effectively blocked OC-like
cell formation in the coculture of the bone marrow cells and NB-19
cells. These results suggested that in the bone microenvironment of
NB-19-bearing mice, the stimulated expression of RANKL plays an
important role in OC formation, leading to osteolytic bone metastasis.
This article has been cited by other articles:
|
|
 |
|
  Y. Fukaya, H. Shimada, L.-C. Wang, E. Zandi, and Y. A. DeClerck Identification of Galectin-3-binding Protein as a Factor Secreted by Tumor Cells That Stimulates Interleukin-6 Expression in the Bone Marrow Stroma J. Biol. Chem., July 4, 2008; 283(27): 18573 - 18581. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Peng, Y. Sohara, R. A. Moats, M. D. Nelson Jr., S. G. Groshen, W. Ye, C. P. Reynolds, and Y. A. DeClerck The Activity of Zoledronic Acid on Neuroblastoma Bone Metastasis Involves Inhibition of Osteoclasts and Tumor Cell Survival and Proliferation Cancer Res., October 1, 2007; 67(19): 9346 - 9355. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Ohno, K. Kubo, H. Murooka, Y. Kobayashi, T. Nishitoba, M. Shibuya, T. Yoneda, and T. Isoe A c-fms tyrosine kinase inhibitor, Ki20227, suppresses osteoclast differentiation and osteolytic bone destruction in a bone metastasis model. Mol. Cancer Ther., November 1, 2006; 5(11): 2634 - 2643. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. M. van Golen, T. S. Schwab, B. Kim, M. E. Soules, S. Su Oh, K. Fung, K. L. van Golen, and E. L. Feldman Insulin-Like Growth Factor-I Receptor Expression Regulates Neuroblastoma Metastasis to Bone. Cancer Res., July 1, 2006; 66(13): 6570 - 6578. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-J. Body, T. Facon, R. E. Coleman, A. Lipton, F. Geurs, M. Fan, D. Holloway, M. C. Peterson, and P. J. Bekker A Study of the Biological Receptor Activator of Nuclear Factor-{kappa}B Ligand Inhibitor, Denosumab, in Patients with Multiple Myeloma or Bone Metastases from Breast Cancer Clin. Cancer Res., February 15, 2006; 12(4): 1221 - 1228. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-J. Kim, H. Uehara, S. Yazici, J. He, R. R. Langley, P. Mathew, D. Fan, and I. J. Fidler Modulation of Bone Microenvironment with Zoledronate Enhances the Therapeutic Effects of STI571 and Paclitaxel against Experimental Bone Metastasis of Human Prostate Cancer Cancer Res., May 1, 2005; 65(9): 3707 - 3715. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Sohara, H. Shimada, C. Minkin, A. Erdreich-Epstein, J. A. Nolta, and Y. A. DeClerck Bone Marrow Mesenchymal Stem Cells Provide an Alternate Pathway of Osteoclast Activation and Bone Destruction by Cancer Cells Cancer Res., February 15, 2005; 65(4): 1129 - 1135. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Zauli, E. Rimondi, V. Nicolin, E. Melloni, C. Celeghini, and P. Secchiero TNF-related apoptosis-inducing ligand (TRAIL) blocks osteoclastic differentiation induced by RANKL plus M-CSF Blood, October 1, 2004; 104(7): 2044 - 2050. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. C. Hofbauer and M. Schoppet Clinical Implications of the Osteoprotegerin/RANKL/RANK System for Bone and Vascular Diseases JAMA, July 28, 2004; 292(4): 490 - 495. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Cheng, M. Kinosaki, M. Takami, Y. Choi, H. Zhang, and R. Murali Disabling of Receptor Activator of Nuclear Factor-{kappa}B (RANK) Receptor Complex by Novel Osteoprotegerin-like Peptidomimetics Restores Bone Loss in Vivo J. Biol. Chem., February 27, 2004; 279(9): 8269 - 8277. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Sohara, H. Shimada, M. Scadeng, H. Pollack, S. Yamada, W. Ye, C. P. Reynolds, and Y. A. DeClerck Lytic Bone Lesions in Human Neuroblastoma Xenograft Involve Osteoclast Recruitment and Are Inhibited by Bisphosphonate Cancer Res., June 15, 2003; 63(12): 3026 - 3031. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Sezer, U. Heider, I. Zavrski, C. A. Kuhne, and L. C. Hofbauer RANK ligand and osteoprotegerin in myeloma bone disease Blood, March 15, 2003; 101(6): 2094 - 2098. [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 |
