Role of RANK, RANKL, OPG, and CXCR4 Tissue Markers in Predicting Bone Metastases in Breast Cancer Patients

Ibrahim, Toni; Sacanna, Emanuele; Gaudio, Michele; Mercatali, Laura; Scarpi, Emanuela; Zoli, Wainer; Serra, Patrizia; Ricci, Rossana; Serra, Luigi; Kang, Yibin; Amadori, Dino

doi:10.1016/j.clbc.2011.05.001

Cited by 45 publications

(36 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…35 Finally, RANK immunohistochemical positivity in combination with CXCR4 positivity identified breast cancer patients whose disease has a high probability to metastasize to bone. 38 Collectively, these observations suggested that sympathetic activation, in response to chronic stress or depression, may transform the bone marrow environment into a favorable tissue for metastatic establishment.…”

Section: Neuroendocrine Factors and Bone Metastasismentioning

confidence: 99%

“…36,37 High CXCR4 expression has also been correlated to poor clinical outcome in patients with breast cancers. 38,39 Similarly, RANKL is expressed by osteoblasts and osteocytes (as well as Tcells and chondrocytes) in bone. Its role in osteoclastogenesis is well established in the setting of bone remodeling as well as osteolytic bone destruction associated with breast metastatic tumors.…”

Section: Neuroendocrine Factors and Bone Metastasismentioning

confidence: 99%

See 1 more Smart Citation

Chronic stress, sympathetic activation and skeletal metastasis of breast cancer cells

Elefteriou¹

2015

BoneKEy Reports

View full text Add to dashboard Cite

Improved detection programs and new therapies significantly improved the 5-year survival rate of women with breast cancer. However, some women still relapse and succumb to cancer because of metastatic disease. In particular, chronically depressed patients do not seem to benefit from newly developed treatments and present with shorter survival. The reason for this association is unclear, but recent cues from preclinical studies point to the possible contribution of neuroendocrine factors generated in response to chronic stress and depression. Retrospective clinical studies also suggest a beneficial effect of sympathetic blockade in terms of less advanced disease at diagnosis, lower cancer-specific mortality, longer disease-free survival and reduced metastasis development and tumor recurrence, especially in patients who have taken propranolol before diagnosis. Therefore, b-blockers or therapies normalizing sympathetic tone might be beneficial as early adjuvant therapies to limit skeletal metastases and growth and eventually to improve prognosis in patients with breast cancers.

show abstract

Section: Neuroendocrine Factors and Bone Metastasismentioning

confidence: 99%

Section: Neuroendocrine Factors and Bone Metastasismentioning

confidence: 99%

Chronic stress, sympathetic activation and skeletal metastasis of breast cancer cells

Elefteriou¹

2015

BoneKEy Reports

View full text Add to dashboard Cite

show abstract

“…Although numerous markers have been evaluated for this purpose, including cross-linked C-terminal telopeptides of type I collagen (ICTP) and cross-linked N-terminal telopeptides of type I collagen (NTX), no really accurate markers have been identified to RANKL: A promising circulating marker for bone metastasis response (13)(14)(15)(16)(17). The present authors previously focused their attention on the molecules of the receptor activator of nuclear factor-κB (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) axis that govern bone resorption and are involved in bone metastasis (18,19). This axis is also probably involved in the early development of metastases (18).…”

Section: Introductionmentioning

confidence: 99%

“…The present authors previously focused their attention on the molecules of the receptor activator of nuclear factor-κB (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) axis that govern bone resorption and are involved in bone metastasis (18,19). This axis is also probably involved in the early development of metastases (18). Briefly, RANKL binds and activates its receptor RANK on the surface of osteoclasts, thus stimulating osteoclast differentiation and maturation, which leads to an increase in bone resorption (20).…”

Section: Introductionmentioning

confidence: 99%

RANKL: A promising circulating marker for bone metastasis response

et al. 2016

Self Cite

View full text Add to dashboard Cite

Abstract. Bone metastases are a frequent event in patients with solid tumors. Although great advances have been made in the treatment of these patients, the identification of novel, accurate indicators of bone response would greatly facilitate the clinical management of the disease. The receptor activator of nuclear factor-κB (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) signaling pathway is significantly involved in bone metastasis formation. The main aim of the present study was to evaluate the role of circulating RANK, RANKL and OPG levels in predicting bone response. Marker accuracy was also compared with that of the conventional tumor marker N-terminal telopeptide of type I collagen (NTX). A prospective study was performed on 49 patients with bone metastases from breast, lung and prostate cancer, who were undergoing treatment with zoledronic acid. Patients were monitored for 1 year with blood tests, clinical evaluation and instrumental exams according to the response evaluation criteria of the University of Texas M. D. Anderson Cancer Center (Houston, TX, USA) and the Positron Emission Tomography Response Criteria in Solid Tumors. Circulating RANK/RANKL/OPG transcripts and NTX levels were evaluated by reverse transcription -quantitative polymerase chain reaction and immune enzymatic assay, respectively. The baseline RANKL levels differed significantly between responders and non-responders, whereas no differences in NTX levels were observed between the two groups. Receiver operating characteristic curve evaluation for all markers revealed that RANKL was the most accurate marker, with an area under the curve of 0.74 (95% confidence interval, 0.54-0.93). In addition, RANKL, which is the target of the novel monoclonal antibody denosumab, was the most accurate predictor of bone response in the present series of patients with bone metastases. Thus, the use of RANKL as a marker could potentially improve clinical practice, as current bone response evaluation is still somewhat problematic. IntroductionBone metastases are common in numerous solid cancers, including breast, prostate and lung cancer (1,2). In the USA, ~2/3 of patients who succumb to cancer each year have bone metastases, and ~20-25% of patients with neoplastic disease develop clinically evident bone metastases during the natural course of the disease (3,4).Bone metastases are responsible for high morbidity and reduced quality of life due to the frequent onset of clinical complications defined as skeletal-related events (SREs), which lead to a reduction in functional independence and quality of life, decrease survival rates and substantially increase healthcare costs (5,6).Bisphosphonates have improved the quality of life of patients with bone metastases from breast cancer by inducing both a reduction in SREs and in the risk of mortality (7). In particular, zoledronic acid (ZA), a potent third-generation nitrogen-containing bisphosphonate, has achieved widespread clinical use in the treatment of bone metastases from solid tumors (8-10). Denosumab, a ...

show abstract

“…A long-term observation of these markers revealed that none of them were able to accurately determine the patient's disease state (16). As aforementioned, the roles of OPG and RANKL have been extensively investigated in the regulation of tumor progression (16,17). The two molecules were shown to be significant in bone regulation (18).…”

Section: Discussionmentioning

confidence: 99%

Serum sRANKL and sRANKL/OPG ratio: Novel biomarkers in non-small cell lung cancer

Sun

Jin

2016

Oncology Letters

View full text Add to dashboard Cite

Abstract. Osteoprotegerin (OPG) and soluble receptor activator of nuclear factor-κB ligand (sRANKL) are bone-regulating molecules. The two molecules have each been indicated to be involved in carcinogenesis. However, the diagnostic significance in non-small cell lung cancer (NSCLC) remains to be investigated. Thus, the objective of the present study was to investigate the serum levels of OPG and sRANKL in NSCLC patients, and to analyze their clinical significance. Serum OPG and sRANKL levels were determined in 50 patients with NSCLC, matched with 25 patients with benign lung nodule and 25 healthy controls by enzyme-linked immunosorbent assay. The level of serum sRANKL and the sRANKL/OPG ratio were significant elevated in the patients with NSCLC compared with the benign lung nodule patients and the healthy controls. Receiver operating characteristic curves were used to evaluate the performance of sRANKL and sRANKL/OPG. When the cut-off values for the sRANKL level and the sRANKL/OPG ratio were set at 4.20 pmol/l and 0.60, respectively, the sensitivity, specificity and accuracy of sRANKL were 74.0, 84.0 and 77.3%, respectively. Moreover, the sensitivity, specificity and accuracy of the sRANKL/OPG ratio were 84.0, 88.0 and 85.3%, respectively. On the other hand, when the cut-off values of the serum sRANKL level and the sRANKL/OPG ratio were set at 5.24 pmol/l and 0.63, respectively, the sensitivity, specificity and accuracy of sRANKL were 60.0, 84.0 and 68.0%, respectively. The sensitivity, specificity and accuracy of the ratio were 78.0, 64.0 and 73.3%, respectively. The OPG/RANKL system may be involved in the pathogenesis of NSCLC. More importantly, the serum sRANKL level and the sRANKL/OPG ratio may have the potential to be novel biomarkers for the diagnosis of NSCLC.

show abstract

Role of RANK, RANKL, OPG, and CXCR4 Tissue Markers in Predicting Bone Metastases in Breast Cancer Patients

Cited by 45 publications

References 38 publications

Chronic stress, sympathetic activation and skeletal metastasis of breast cancer cells

Chronic stress, sympathetic activation and skeletal metastasis of breast cancer cells

RANKL: A promising circulating marker for bone metastasis response

Serum sRANKL and sRANKL/OPG ratio: Novel biomarkers in non-small cell lung cancer

Contact Info

Product

Resources

About