A quantitative model for spontaneous bone metastasis: evidence for a mitogenic effect of bone on Walker 256 cancer cells

Kostenuik, Paul J.; Singh, Gurmit; Suyama, Kaye; Orr, F. W.

doi:10.1007/bf00133469

Cited by 26 publications

(12 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This provided clues as to possible mechanisms for tumor cell osteotropism, and shortly thereafter it was reported that bone resorption in bone organ cultures stimulated the proliferation of tumor cells that possessed bone metastasizing properties (301). Consistent with these culture studies, it was subsequently shown in rats that cancer cells immediately adjacent to bone surfaces had significantly greater proliferation rates compared with those that were distant from bone (302). Stimulation of bone resorption was shown to specifically increase the proliferation rate of metastatic cancer cells in bone, but not in other tissues (303).…”

Section: G Rankl and Rankl Inhibition In Bone Metastasis And Multiplsupporting

confidence: 65%

Receptor Activator of Nuclear Factor κB Ligand and Osteoprotegerin Regulation of Bone Remodeling in Health and Disease

2007

Self Cite

View full text Add to dashboard Cite

Osteoclasts and osteoblasts dictate skeletal mass, structure, and strength via their respective roles in resorbing and forming bone. Bone remodeling is a spatially coordinated lifelong process whereby old bone is removed by osteoclasts and replaced by bone-forming osteoblasts. The refilling of resorption cavities is incomplete in many pathological states, which leads to a net loss of bone mass with each remodeling cycle. Postmenopausal osteoporosis and other conditions are associated with an increased rate of bone remodeling, which leads to accelerated bone loss and increased risk of fracture. Bone resorption is dependent on a cytokine known as RANKL (receptor activator of nuclear factor B ligand), a TNF family member that is essential for osteoclast formation, activity, and survival in normal and pathological states of bone remodeling. The catabolic effects of RANKL are prevented by osteoprotegerin (OPG), a TNF receptor family member that binds RANKL and thereby prevents activation of its single cognate receptor called RANK. Osteoclast activity is likely to depend, at least in part, on the relative balance of RANKL and OPG. Studies in numerous animal models of bone disease show that RANKL inhibition leads to marked suppression of bone resorption and increases in cortical and cancellous bone volume, density, and strength. RANKL inhibitors also prevent focal bone loss that occurs in animal models of rheumatoid arthritis and bone metastasis. Clinical trials are exploring the effects of denosumab, a fully human anti-RANKL antibody, on bone loss in patients with osteoporosis, bone metastasis, myeloma, and rheumatoid arthritis. (Endocrine Reviews 29: 2008)

show abstract

Section: G Rankl and Rankl Inhibition In Bone Metastasis And Multiplsupporting

confidence: 65%

Receptor Activator of Nuclear Factor κB Ligand and Osteoprotegerin Regulation of Bone Remodeling in Health and Disease

2007

Self Cite

View full text Add to dashboard Cite

show abstract

“…Various techniques of experimental bone metastasis in animals have been developed throughout the years and include injection of tumour cells directly into (1) the intramedullary cavity (Galasko & Bennett 1976), (2) abdominal aorta (Powles et al 1973), (3) tail vein with inferior vena cava occlusion (Shevrin et al 1988), (4) left upper thigh muscle (Kostenuik et al 1992), (5) left thoracic artery with renal artery occlusion and (6) left cardiac ventricle (Arguello et al 1988, Nakai et al 1992.…”

Section: Local Tumour Syndromes In Bonementioning

confidence: 99%

Hypercalcaemia of malignancy and basic research on mechanisms responsible for osteolytic and osteoblastic metastasis to bone

Clines

Guise²

2005

Endocr Relat Cancer

228

211

View full text Add to dashboard Cite

Calcium homeostasis is a tightly regulated process involving the co-ordinated efforts of the skeleton, kidney, parathyroid glands and intestine. Neoplasms can alter this homeostasis indirectly through the production of endocrine factors resulting in humoral hypercalcaemia of malignancy. Relatively common with breast and lung cancer, this paraneoplastic condition is most often due to tumour production of parathyroid hormone-related protein and ensuing increased osteoclastic bone resorption. Although control of hypercalcaemia is generally successful, the development of this complication is associated with a poor prognosis. The metastasis of tumour cells to bone represents another skeletal complication of malignancy. As explained in the 'seed and soil' hypothesis, bone represents a fertile ground for cancer cells to flourish. The molecular mechanisms of this mutually beneficial relationship between bone and cancer cells are beginning to be understood. In the case of osteolytic bone disease, tumour-produced parathyroid hormone-related protein stimulates osteoclasts that in turn secrete tumour-activating transforming growth factor-b that further stimulates local cancer cells. This 'vicious cycle' of bone metastases represents reciprocal bone/ cancer cellular signals that likely modulate osteoblastic bone metastatic lesions as well. The development of targeted therapies to either block initial cancer cell chemotaxis, invasion and adhesion or to break the 'vicious cycle' is dependent on a more complete understanding of bone metastases. Although bisphosphonates delay progression of skeletal metastases, it is clear that more effective therapies are needed. Cancer-associated bone morbidity remains a major public health problem, and to improve therapy and prevention it is important to understand the pathophysiology of the effects of cancer on bone. This review will detail scientific advances regarding this area.

show abstract

“…As outlined, this leads to increased osteoclast differentiation; resulting bone resorption mobilizes growth factors, such as transforming growth factor beta (TGF-b), insulin-like growth factor, basic fibroblast growth factor and bone morphogenetic protein (BMP) from the bone matrix. Those cytokines in turn stimulate tumour proliferation and support tumour cell survival [Yin et al 2005;Roodman, 2004;Kostenuik et al 1992;Hauschka et al 1986] (Figure 1). …”

Section: Rank/rankl/opg Pathway In Breast Cancer Bone Metastasesmentioning

confidence: 99%

Denosumab for the treatment of bone metastases in breast cancer: evidence and opinion

Steger

Bartsch

2011

Ther Adv Med Oncol

View full text Add to dashboard Cite

Abstract:Introduction: Denosumab, a fully human monoclonal antibody, targets the receptor activator of nuclear factor-kappaB (RANK) ligand, a protein essential for osteoclast differentiation, activity and survival. Loss of osteoclasts from the bone surface reduces bone turnover and bone loss in malignant and benign diseases. In breast cancer, bone metastases are frequently observed; cancer treatment-induced bone loss (CTIBL) may result as a consequence of endocrine treatment or chemotherapy. Furthermore, preclinical studies suggest a direct role of the RANK/RANK-ligand pathway in breast tumorigenesis. This paper reviews preclinical and clinical data on denosumab in breast cancer. Materials and methods: Studies were identified through the Medline database. Key search terms included: AMG-162, bisphosphonates, denosumab, RANK-ligand and zoledronic acid. Information available in abstract form only was retrieved from major oncology meetings, such as the American Society of Clinical Oncology (ASCO) annual meeting, ASCO breast meeting, European Cancer Organization, European Society of Medical Oncology and the San Antonio Breast Cancer Symposium. Results: Denosumab was consistently well tolerated throughout clinical trials, although the observed incidence of osteonecrosis of the jaw was comparable to that with bisphosphonates. Efficacy as determined by a reduction of skeletal-related events was at least equal to zoledronic acid, and superior in one phase III study conducted in patients with metastatic breast cancer. Clinical trials investigating the role of denosumab for the prevention of CTIBL and breast cancer recurrences are currently ongoing. Conclusion: In conclusion, denosumab appears to be an effective and safe treatment option in patients with bone metastases from breast cancer with the potential of also preventing CTIBL.

show abstract

A quantitative model for spontaneous bone metastasis: evidence for a mitogenic effect of bone on Walker 256 cancer cells

Cited by 26 publications

References 21 publications

Receptor Activator of Nuclear Factor κB Ligand and Osteoprotegerin Regulation of Bone Remodeling in Health and Disease

Receptor Activator of Nuclear Factor κB Ligand and Osteoprotegerin Regulation of Bone Remodeling in Health and Disease

Hypercalcaemia of malignancy and basic research on mechanisms responsible for osteolytic and osteoblastic metastasis to bone

Denosumab for the treatment of bone metastases in breast cancer: evidence and opinion

Contact Info

Product

Resources

About