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RANKL/RANK/OPG system beyond bone remodeling: involvement in breast cancer and clinical perspectives

Published on Dec 1, 2019in Journal of Experimental & Clinical Cancer Research5.646
路 DOI :10.1186/s13046-018-1001-2
Marco Infante2
Estimated H-index: 2
,
Alessandra Fabi30
Estimated H-index: 30
+ 3 AuthorsAndreaFabbri41
Estimated H-index: 41
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Abstract
RANKL/RANK/OPG system consists of three essential signaling molecules: i) the receptor activator of nuclear factor (NF)-kB-ligand (RANKL), ii) the receptor activator of NF-kB (RANK), and iii) the soluble decoy receptor osteoprotegerin (OPG). Although this system is critical for the regulation of osteoclast differentiation/activation and calcium release from the skeleton, different studies have elucidated its specific role in mammary gland physiology and hormone-driven epithelial proliferation during pregnancy. Of note, several data suggest that progesterone induces mammary RANKL expression in mice and humans. In turn, RANKL controls cell proliferation in breast epithelium under physiological conditions typically associated with higher serum progesterone levels, such as luteal phase of the menstrual cycle and pregnancy. Hence, RANKL/RANK system can be regarded as a major downstream mediator of progesterone-driven mammary epithelial cells proliferation, potentially contributing to breast cancer initiation and progression. Expression of RANKL, RANK, and OPG has been detected in breast cancer cell lines and in human primary breast cancers. To date, dysregulation of RANKL/RANK/OPG system at the skeletal level has been widely documented in the context of metastatic bone disease. In fact, RANKL inhibition through the RANKL-blocking human monoclonal antibody denosumab represents a well-established therapeutic option to prevent skeletal-related events in metastatic bone disease and adjuvant therapy-induced bone loss in breast cancer. On the other hand, the exact role of OPG in breast tumorigenesis is still unclear. This review focuses on molecular mechanisms linking RANKL/RANK/OPG system to mammary tumorigenesis, highlighting pre-clinical and clinical evidence for the potential efficacy of RANKL inhibition as a prevention strategy and adjuvant therapy in breast cancer settings.
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#1Tilman D. Rachner (DKFZ: German Cancer Research Center)H-Index: 18
#2Sabine Kasimir-Bauer (University of Duisburg-Essen)H-Index: 25
Last. Ann-Kathrin Bittner (University of Duisburg-Essen)H-Index: 4
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Background: We assessed serum concentrations of the receptor activator of nuclear factor kappa-B ligand (RANKL) and its decoy receptor osteoprotegerin (OPG), two proteins implicated in the development and progression of breast cancer (BC), in 509 patients with primary, non-metastatic BC. Then the results were evaluated with regards to the occurrence of bone metastases, the presence of disseminated tumor cells (DTC) in the bone marrow, survival and risk of developing metastatic disease. Patients ...
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#1Anastasios D. Papanastasiou (University of Patras)H-Index: 12
#2Chaido Sirinian (University of Patras)H-Index: 7
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After the publication of this article [1] we noticed that in Fig.聽1, the gel images (1A and 1B lower panel) were incorrect.
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This project was funded by research grant #111454 from the Deutsche Kresbshilfe. RT Fortner was supported by a Marie Curie International Incoming Fellowship of the European Commission鈥檚 Seventh Framework Programme (MC-IIF-623984). The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle...
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Abstract Background To this day, empirical data suggests that zinc has important roles in matrix synthesis, bone turnover, and mineralization and its beneficial effects on bone could be mediated through different mechanisms. The influence of zinc on bone turnover could be facilitated via regulating RANKL/RANK/OPG pathway in bone tissue. Therefore, the aim of the study was to conduct a review to investigate the possible effect of the zinc mediated bone remodeling via RANKL/RANK/OPG pathway. Metho...
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