Access the full text.
Sign up today, get DeepDyve free for 14 days.
J. Healey, Holly Brown (2000)
Complications of bone metastasesCancer, 88
P. Bekker, D. Holloway, Amy Rasmussen, Robyn Murphy, Steven Martin, P. Leese, Gregory Holmes, C. Dunstan, A. DePaoli (2004)
A Single‐Dose Placebo‐Controlled Study of AMG 162, a Fully Human Monoclonal Antibody to RANKL, in Postmenopausal WomenJournal of Bone and Mineral Research, 19
T. Burgess, Y. Qian, S. Kaufman, B. Ring, G. Van, Charles Capparelli, M. Kelley, H. Hsu, W. Boyle, C. Dunstan, Sylvia Hu, D. Lacey (1999)
The Ligand for Osteoprotegerin (OPGL) Directly Activates Mature OsteoclastsThe Journal of Cell Biology, 145
(2006)
RANKL infusion as a disease model : Implications for bone and vascular systems
A. Parfitt, M. Drezner, F. Glorieux, J. Kanis, H. Malluche, Pierre Meunier, S. Ott, R. Recker (1987)
Bone histomorphometry: Standardization of nomenclature, symbols, and units: Report of the asbmr histomorphometry nomenclature committeeJournal of Bone and Mineral Research, 2
N. Kohno, K. Aogi, H. Minami, Seigo Nakamura, T. Asaga, Y. Iino, Toru Watanabe, C. Goessl, Y. Ohashi, S. Takashima (2005)
Zoledronic acid significantly reduces skeletal complications compared with placebo in Japanese women with bone metastases from breast cancer: a randomized, placebo-controlled trial.Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 23 15
A. Pataki, K. Müller, J. Green, Y. Ma, Qing Li, W. Jee (1997)
Effects of short‐term treatment with the bisphosphonates zoledronate and pamidronate on rat bone: A comparative histomorphometric study on the cancellous bone formed before, during, and after treatmentThe Anatomical Record, 249
(1998)
Bisphosphonates : mechanism of action
J. Fisher, M. Rogers, J. Halasy, S. Luckman, D. Hughes, P. Masarachia, G. Wesolowski, R. Russell, G. Rodan, A. Reszka (1999)
Alendronate mechanism of action: geranylgeraniol, an intermediate in the mevalonate pathway, prevents inhibition of osteoclast formation, bone resorption, and kinase activation in vitro.Proceedings of the National Academy of Sciences of the United States of America, 96 1
S. Morony, C. Capparelli, Richard Lee, G. Shimamoto, T. Boone, D. Lacey, C. Dunstan (1999)
A Chimeric Form of Osteoprotegerin Inhibits Hypercalcemia and Bone Resorption Induced by IL‐1β, TNF‐α, PTH, PTHrP, and 1,25(OH)2D3Journal of Bone and Mineral Research, 14
P. Phadke, R. Mercer, J. Harms, Yujiang Jia, A. Frost, Jennifer Jewell, K. Bussard, S. Nelson, Cynthia Moore, J. Kappes, C. Gay, A. Mastro, D. Welch (2006)
Kinetics of Metastatic Breast Cancer Cell Trafficking in BoneClinical Cancer Research, 12
(2007)
resorption , rather than direct cytotoxicity , mediates the anti - tumor actions of ibandronate and osteoprotegerin in a murine model of breast cancer bone metastasis
S. Kitazawa, R. Kitazawa (2002)
RANK ligand is a prerequisite for cancer‐associated osteolytic lesionsThe Journal of Pathology, 198
(2007)
metastasis process
C. Morrissey, Paul Kostenuik, L. Brown, R. Vessella, E. Corey (2007)
Host-derived RANKL is responsible for osteolysis in a C4-2 human prostate cancer xenograft model of experimental bone metastasesBMC Cancer, 7
C. Galasko (1976)
Mechanisms of bone destruction in the development of skeletal metastasesNature, 263
L. Schneeweis, D. Willard, M. Milla (2005)
Functional Dissection of Osteoprotegerin and Its Interaction with Receptor Activator of NF-κB Ligand*Journal of Biological Chemistry, 280
Giovanni Abbadessa, Giovanni Masci (2005)
Vascular endothelial growth factor acts as an osteolytic factor in breast cancer metastases to boneBritish Journal of Cancer, 92
A. Mancino, V. Klimberg, Matsuo Yamamoto, S. Manolagas, Etsuko Abe (2001)
Breast cancer increases osteoclastogenesis by secreting M-CSF and upregulating RANKL in stromal cells.The Journal of surgical research, 100 1
N. Bucay, I. Sarosi, C. Dunstan, S. Morony, J. Tarpley, C. Capparelli, S. Scully, H. Tan, Wei-wei Xu, D. Lacey, W. Boyle, W. Simonet (1998)
osteoprotegerin-deficient mice develop early onset osteoporosis and arterial calcification.Genes & development, 12 9
Noriko Chikatsu, Yasuhiro Takeuchi, Y. Tamura, Seiji Fukumoto, K. Yano, E. Tsuda, Etsuro Ogata, T. Fujita (2000)
Interactions between cancer and bone marrow cells induce osteoclast differentiation factor expression and osteoclast-like cell formation in vitro.Biochemical and biophysical research communications, 267 2
R. Theriault, A. Lipton, G. Hortobagyi, R. Leff, S. Glück, J. Stewart, Sean Costello, I. Kennedy, Joseph Simeone, J. Seaman, Robert Knight, K. Mellars, M. Heffernan, D. Reitsma (1999)
Pamidronate reduces skeletal morbidity in women with advanced breast cancer and lytic bone lesions: a randomized, placebo-controlled trial. Protocol 18 Aredia Breast Cancer Study Group.Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 17 3
S. Paget (1989)
The distribution of secondary growths in cancer of the breast. 1889.Cancer metastasis reviews, 8 2
(2000)
and osteolytic bone metastases - long term follow up of two randomized controlled trials
A. Lipton, R. Theriault, G. Hortobagyi, Joseph Simeone, Robert Knight, K. Mellars, D. Reitsma, M. Heffernan, J. Seaman (2000)
Pamidronate prevents skeletal complications and is effective palliative treatment in women with breast carcinoma and osteolytic bone metastasesCancer, 88
A. Mizuno, N. Amizuka, K. Irie, A. Murakami, N. Fujise, Takeshi Kanno, Yasushi Sato, N. Nakagawa, H. Yasuda, S. Mochizuki, T. Gomibuchi, K. Yano, N. Shima, N. Washida, E. Tsuda, T. Morinaga, K. Higashio, H. Ozawa (1998)
Severe osteoporosis in mice lacking osteoclastogenesis inhibitory factor/osteoprotegerin.Biochemical and biophysical research communications, 247 3
R. Coleman (2001)
Metastatic bone disease: clinical features, pathophysiology and treatment strategies.Cancer treatment reviews, 27 3
R. Coleman, R. Rubens (1987)
The clinical course of bone metastases from breast cancer.British Journal of Cancer, 55
W. Orr, J. Varani, MK Gondex, P. Ward, G. Mundy (1979)
Chemotactic responses of tumor cells to products of resorbing bone.Science, 203 4376
(2005)
inhibition of
P. Conte, J. Latreille, L. Mauriac, F. Calabresi, R. Santos, D. Campos, J. Bonneterre, G. Francini, J. Ford (1996)
Delay in progression of bone metastases in breast cancer patients treated with intravenous pamidronate: results from a multinational randomized controlled trial. The Aredia Multinational Cooperative Group.Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 14 9
G. Hortobagyi, R. Theriault, A. Lipton, L. Porter, D. Blayney, C. Sinoff, H. Wheeler, Joseph Simeone, J. Seaman, Robert Knight, M. Heffernan, K. Mellars, D. Reitsma (1998)
Long-term prevention of skeletal complications of metastatic breast cancer with pamidronate. Protocol 19 Aredia Breast Cancer Study Group.Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 16 6
Rachel Thomas, T. Guise, J. Yin, J. Elliott, N. Horwood, T. Martin, M. Gillespie, S. Vincent
Breast Cancer Cells Interact with Osteoblasts to Support Osteoclast Formation*
N. Bravenboer, S. Papapoulos, P. Holzmann, N. Hamdy, J. Netelenbos, P. Lips (1999)
Bone Histomorphometric Evaluation of Pamidronate Treatment in Clinically Manifest OsteoporosisOsteoporosis International, 9
(2005)
Soluble RANKL has detrimental effects on cortical and trabecular bone volume , mineralization and bone strength in mice
R. Hultborn, S. Gundersen, S. Rydén, E. Holmberg, J. Carstensen, U. Wallgren, S. Killany, L. Andreassen, G. Carlsson, N. Fahl, T. Hatschek, H. Sommer, Y. Hessman, B. Hornmark-Stenstam, S. Johnsborg, R. Klepp, R. Laiño, L. Niklasson, C. Rudenstam, A. Sundbeck, M. Söderberg, G. Tejler (1999)
Efficacy of pamidronate in breast cancer with bone metastases: a randomized, double-blind placebo-controlled multicenter study.Anticancer research, 19 4C
D. Santini, B. Vincenzi, G. Dicuonzo, G. Avvisati, C. Massacesi, F. Battistoni, M. Gavasci, L. Rocci, M. Tirindelli, V. Altomare, M. Tocchini, M. Bonsignori, G. Tonini (2003)
Zoledronic acid induces significant and long-lasting modifications of circulating angiogenic factors in cancer patients.Clinical cancer research : an official journal of the American Association for Cancer Research, 9 8
Elizabeth O'Brien, Elizabeth O'Brien, John Williams, M. Marshall (2000)
Osteoprotegerin ligand regulates osteoclast adherence to the bone surface in mouse calvaria.Biochemical and biophysical research communications, 274 2
P. Chavassieux, M. Arlot, C. Reda, Lynn Wei, A. Yates, P. Meunier (1997)
Histomorphometric assessment of the long-term effects of alendronate on bone quality and remodeling in patients with osteoporosis.The Journal of clinical investigation, 100 6
Janna Quinn, L. Brown, Jian Zhang, E. Keller, R. Vessella, E. Corey (2005)
Comparison of Fc-osteoprotegerin and zoledronic acid activities suggests that zoledronic acid inhibits prostate cancer in bone by indirect mechanismsProstate Cancer and Prostatic Diseases, 8
C. Poznak, S. Cross, M. Saggese, C. Hudis, K. Panageas, L. Norton, R. Coleman, I. Holen (2006)
Expression of osteoprotegerin (OPG), TNF related apoptosis inducing ligand (TRAIL), and receptor activator of nuclear factor κB ligand (RANKL) in human breast tumoursJournal of Clinical Pathology, 59
E. Waterman, N. Cross, J. Lippitt, S. Cross, I. Rehman, I. Holen, F. Hamdy, C. Eaton (2007)
The antibody MAB8051 directed against osteoprotegerin detects carbonic anhydrase II: Implications for association studies with human cancersInternational Journal of Cancer, 121
D. Lacey, E. Timms, H. Tan, M. Kelley, C. Dunstan, Tim Burgess, R. Elliott, A. Colombero, G. Elliott, S. Scully, H. Hsu, J. Sullivan, N. Hawkins, E. Davy, Charles Capparelli, A. Eli, Y. Qian, S. Kaufman, I. Sarosi, V. Shalhoub, G. Senaldi, Jane Guo, J. Delaney, W. Boyle (1998)
Osteoprotegerin Ligand Is a Cytokine that Regulates Osteoclast Differentiation and ActivationCell, 93
Midori Nakamura, N. Udagawa, S. Matsuura, M. Mogi, Hiroshi Nakamura, H. Horiuchi, N. Saito, B. Hiraoka, Yasuhiro Kobayashi, K. Takaoka, H. Ozawa, H. Miyazawa, N. Takahashi (2003)
Osteoprotegerin regulates bone formation through a coupling mechanism with bone resorption.Endocrinology, 144 12
Y. Yuan, P. Kostenuik, M. Ominsky, S. Morony, S. Adamu, D. Simionescu, D. Basalyga, F. Asuncion, T. Bateman (2008)
Skeletal deterioration induced by RANKL infusion: a model for high-turnover bone diseaseOsteoporosis International, 19
G. Mundy, L. Raisz, R. Cooper, G. Schechter, S. Salmon (1974)
Evidence for the secretion of an osteoclast stimulating factor in myeloma.The New England journal of medicine, 291 20
J. Ferlay, P. Pisani, D. Parkin (2001)
Globocan 2000 : cancer incidence, mortality and prevalence worldwide
S. Yaccoby, R. Pearse, C. Johnson, B. Barlogie, Yongwon Choi, J. Epstein (2002)
Myeloma interacts with the bone marrow microenvironment to induce osteoclastogenesis and is dependent on osteoclast activityBritish Journal of Haematology, 116
D. Lacey, H. Tan, John Lu, S. Kaufman, G. Van, Wanrang Qiu, Alana Rattan, S. Scully, F. Fletcher, T. Juan, M. Kelley, T. Burgess, W. Boyle, A. Polverino (2000)
Osteoprotegerin ligand modulates murine osteoclast survival in vitro and in vivo.The American journal of pathology, 157 2
Kostenuik Pj (2004)
Revisiting the seed and soil theory of bone metastasis: new tools, same answer.Journal of Musculoskeletal & Neuronal Interactions, 4
T. Plunkett, Philip Smith, R. Rubens (2000)
Risk of complications from bone metastases in breast cancer. implications for management.European journal of cancer, 36 4
The benefits of bisphosphonates (BPs) in reducing skeletal-related events (SREs) in patients with bone metastases has mainly been attributed to their potent osteoclast inhibiting effect. However, despite the use of modern systemic anticancer therapy including potent BPs, many patients with bone metastases continue to have SREs. An improved understanding of the fundamental mechanisms of bone destruction allows for further development of appropriate targeted treatments. In this study, archival paraffin-embedded bone metastases specimens from patients with metastatic breast cancer were examined for the presence of osteoclasts, expression of the receptor activator of nuclear factor κB (RANK), RANK Ligand (RANKL), osteoprotegerin (OPG) and vascular endothelial growth factor (VEGF). Histological specimens were available for primary breast cancer, lymph node metastases, normal breast and normal bone tissues for comparison. Bone metastasis specimens were available for 20 BP naïve patients and two BP-treated patients. Osteoclasts were significantly increased in the bone metastases of the BP naïve group compared to normal bone. No osteoclasts were detected in the BP-treated group. RANKL was predominantly expressed in osteoblasts and in the stromal elements of metastatic tissue. Conversely, RANK was present in osteoclasts of bone metastases and normal bone, as well as in tumor cells of metastatic lymph nodes and bone metastases. VEGF was strongly expressed in the control bone and bone metastases regardless of BP treatment. In summary, osteoclasts may not be the singular obligatory factor for osteolysis in bone metastases. An increased expression of RANKL in stromal tissue surrounding bone metastases, RANK in osteoclasts and VEGF may serve as future targeted therapies possibly in conjunction with bisphosphonates. The mechanisms for osteoclast expression and the expression of RANKL, RANK, OPG and VEGF merit further prospective analysis, particularly in the context of BP treatment and progressive bone metastases.
Oncology Reports – Spandidos Publications
Published: May 1, 2009
Read and print from thousands of top scholarly journals.
Already have an account? Log in
Bookmark this article. You can see your Bookmarks on your DeepDyve Library.
To save an article, log in first, or sign up for a DeepDyve account if you don’t already have one.
Copy and paste the desired citation format or use the link below to download a file formatted for EndNote
Access the full text.
Sign up today, get DeepDyve free for 14 days.
All DeepDyve websites use cookies to improve your online experience. They were placed on your computer when you launched this website. You can change your cookie settings through your browser.