{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T22:44:40Z","timestamp":1792363480719,"version":"4.4.0"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2020,4,7]],"date-time":"2020-04-07T00:00:00Z","timestamp":1586217600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"DOI":"10.3389\/fonc.2020.00462","type":"journal-article","created":{"date-parts":[[2020,4,7]],"date-time":"2020-04-07T04:36:50Z","timestamp":1586234210000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":21,"title":["Osteoprotegerin: Relationship to Breast Cancer Risk and Prognosis"],"prefix":"10.3389","volume":"10","author":[{"given":"Dirk","family":"Geerts","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Chopra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Connelly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2020,4,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"42777","DOI":"10.18632\/oncotarget.8658","article-title":"Osteoprotegerin rich tumor microenvironment: implications in breast cancer","volume":"7","author":"Goswami","year":"2016","journal-title":"Oncotarget"},{"key":"B2","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1186\/s12943-015-0390-5","article-title":"Osteoprotegerin in breast cancer: beyond bone remodeling","volume":"14","author":"Weichhaus","year":"2015","journal-title":"Mol Cancer"},{"key":"B3","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1016\/S0092-8674(00)80209-3","article-title":"Osteoprotegerin: a novel secreted protein involved in the regulation of bone density","volume":"89","author":"Simonet","year":"1997","journal-title":"Cell"},{"key":"B4","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1006\/bbrc.1997.6603","article-title":"Isolation of a novel cytokine from human fibroblasts that specifically inhibits osteoclastogenesis","volume":"234","author":"Tsuda","year":"1997","journal-title":"Biochem Biophys Res Commun"},{"key":"B5","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1007\/s10549-005-2419-8","article-title":"Osteoprotegerin (OPG) expression by breast cancer cells in vitro and breast tumours in vivo\u2013a role in tumour cell survival?","volume":"92","author":"Holen","year":"2005","journal-title":"Breast Cancer Res Treat"},{"key":"B6","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1002\/jcb.22232","article-title":"Osteoprotegerin production by breast cancer cells is suppressed by dexamethasone and confers resistance against TRAIL-induced apoptosis","volume":"108","author":"Rachner","year":"2009","journal-title":"J Cell Biochem"},{"key":"B7","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1186\/s13046-018-1001-2","article-title":"RANKL\/RANK\/OPG system beyond bone remodeling: involvement in breast cancer and clinical perspectives","volume":"38","author":"Infante","year":"2019","journal-title":"J Exp Clin Cancer Res"},{"key":"B8","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1046\/j.1432-1327.1998.2540685.x","article-title":"Cloning and characterization of the gene encoding human osteoprotegerin\/osteoclastogenesis-inhibitory factor","volume":"254","author":"Morinaga","year":"1998","journal-title":"Eur J Biochem"},{"key":"B9","doi-asserted-by":"publisher","first-page":"4080","DOI":"10.1210\/jc.2002-020124","article-title":"Sequence variations in the osteoprotegerin gene promoter in patients with postmenopausal osteoporosis","volume":"87","author":"Arko","year":"2002","journal-title":"J Clin Endocrinol Metab"},{"key":"B10","doi-asserted-by":"publisher","first-page":"1245","DOI":"10.1359\/jbmr.2002.17.7.1245","article-title":"Polymorphisms in the osteoprotegerin gene are associated with osteoporotic fractures","volume":"17","author":"Langdahl","year":"2002","journal-title":"J Bone Miner Res"},{"key":"B11","doi-asserted-by":"publisher","first-page":"1519","DOI":"10.1007\/s00198-005-1865-9","article-title":"The influence of Lys3Asn polymorphism in the osteoprotegerin gene on bone mineral density in Chinese postmenopausal women","volume":"16","author":"Zhao","year":"2005","journal-title":"Osteoporos Int"},{"key":"B12","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1186\/1471-2407-13-40","article-title":"Genetic polymorphism of the OPG gene associated with breast cancer","volume":"13","author":"Ney","year":"2013","journal-title":"BMC Cancer"},{"key":"B13","doi-asserted-by":"publisher","first-page":"1563","DOI":"10.1007\/s00198-015-3029-x","article-title":"RANKL and OPG gene polymorphisms: associations with vertebral fractures and bone mineral density in premenopausal systemic lupus erythematosus","volume":"26","author":"Bonfa","year":"2015","journal-title":"Osteoporos Int"},{"key":"B14","doi-asserted-by":"publisher","first-page":"702","DOI":"10.3892\/etm.2016.3342","article-title":"OPG rs2073617 polymorphism is associated with upregulated OPG protein expression and an increased risk of intervertebral disc degeneration","volume":"12","author":"Xue","year":"2016","journal-title":"Exp Ther Med"},{"key":"B15","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1007\/s11010-015-2352-z","article-title":"The association between RANKL and osteoprotegerin gene polymorphisms with breast cancer","volume":"403","author":"Omar","year":"2015","journal-title":"Mol Cell Biochem"},{"key":"B16","doi-asserted-by":"publisher","first-page":"e220","DOI":"10.1016\/j.clbc.2018.09.004","article-title":"Association of SNP-SNP interactions between RANKL, OPG, CHI3L1, and VDR genes with breast cancer risk in Egyptian women","volume":"19","author":"Shaker","year":"2019","journal-title":"Clin Breast Cancer"},{"key":"B17","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1007\/s10654-014-9975-3","article-title":"Serum osteoprotegerin and future risk of cancer and cancer-related mortality in the general population: the tromso study","volume":"30","author":"Vik","year":"2015","journal-title":"Eur J Epidemiol"},{"key":"B18","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1186\/s12916-017-0786-8","article-title":"Osteoprotegerin and breast cancer risk by hormone receptor subtype: a nested case-control study in the EPIC cohort","volume":"15","author":"Fortner","year":"2017","journal-title":"BMC Med"},{"key":"B19","doi-asserted-by":"publisher","first-page":"2152","DOI":"10.1016\/j.ajpath.2017.04.022","article-title":"Breast cancer molecular stratification: from intrinsic subtypes to integrative clusters","volume":"187","author":"Russnes","year":"2017","journal-title":"Am J Pathol"},{"key":"B20","doi-asserted-by":"publisher","first-page":"3811","DOI":"10.18632\/oncotarget.14013","article-title":"Aberrant regulation of RANKL\/OPG in women at high risk of developing breast cancer","volume":"8","author":"Kiechl","year":"2017","journal-title":"Oncotarget"},{"key":"B21","doi-asserted-by":"publisher","first-page":"1010","DOI":"10.1186\/s12885-018-4887-3","article-title":"Receptor activator of nuclear factor kB ligand, osteoprotegerin, and risk of death following a breast cancer diagnosis: results from the EPIC cohort","volume":"18","author":"Sarink","year":"2018","journal-title":"BMC Cancer"},{"key":"B22","doi-asserted-by":"publisher","first-page":"933","DOI":"10.1038\/nm.4118","article-title":"RANK ligand as a potential target for breast cancer prevention in BRCA1-mutation carriers","volume":"22","author":"Nolan","year":"2016","journal-title":"Nat Med"},{"key":"B23","doi-asserted-by":"publisher","first-page":"86687","DOI":"10.18632\/oncotarget.13417","article-title":"Plasma osteoprotegerin and breast cancer risk in BRCA1 and BRCA2 mutation carriers","volume":"7","author":"Oden","year":"2016","journal-title":"Oncotarget"},{"key":"B24","doi-asserted-by":"publisher","first-page":"1331","DOI":"10.1016\/j.ebiom.2015.08.037","article-title":"Osteoprotegerin (OPG), the endogenous inhibitor of receptor activator of NF-\u03baB ligand (RANKL), is dysregulated in BRCA mutation carriers","volume":"2","author":"Widschwendter","year":"2015","journal-title":"EBioMed"},{"key":"B25","doi-asserted-by":"publisher","first-page":"716","DOI":"10.1136\/jcp.2005.030031","article-title":"Expression of receptor activator of nuclear factor kappabeta ligand (RANKL) and tumour necrosis factor related, apoptosis inducing ligand (TRAIL) in breast cancer, and their relations with osteoprotegerin, oestrogen receptor, and clinicopathological variables","volume":"59","author":"Cross","year":"2006","journal-title":"J Clin Pathol"},{"key":"B26","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1136\/jcp.2005.026534","article-title":"Expression of osteoprotegerin (OPG), TNF related apoptosis inducing ligand (TRAIL), and receptor activator of nuclear factor kappaB ligand (RANKL) in human breast tumours","volume":"59","author":"Van Poznak","year":"2006","journal-title":"J Clin Pathol"},{"key":"B27","doi-asserted-by":"publisher","first-page":"e19234","DOI":"10.1371\/journal.pone.0019234","article-title":"Receptor activator of NF-kB (RANK) expression in primary tumors associates with bone metastasis occurrence in breast cancer patients","volume":"6","author":"Santini","year":"2011","journal-title":"PLoS ONE"},{"key":"B28","first-page":"199","article-title":"Expression profile of receptor activator of nuclear-kappaB (RANK), RANK ligand (RANKL) and osteoprotegerin (OPG) in breast cancer","volume":"33","author":"Owen","year":"2013","journal-title":"Anticancer Res"},{"key":"B29","doi-asserted-by":"publisher","first-page":"1196","DOI":"10.1016\/j.molonc.2014.04.003","article-title":"OPG and PgR show similar cohort specific effects as prognostic factors in ER positive breast cancer","volume":"8","author":"Sanger","year":"2014","journal-title":"Mol Oncol"},{"key":"B30","doi-asserted-by":"publisher","first-page":"807","DOI":"10.1002\/jso.23737","article-title":"Expression of receptor activator of nuclear factor \u03ba-B as a poor prognostic marker in breast cancer","volume":"110","author":"Park","year":"2014","journal-title":"J Surg Oncol"},{"key":"B31","doi-asserted-by":"publisher","first-page":"93","DOI":"10.3322\/caac.21388","article-title":"The eighth edition AJCC cancer staging manual: continuing to build a bridge from a population-based to a more \u201cpersonalized\u201d approach to cancer staging","volume":"67","author":"Amin","year":"2017","journal-title":"CA Cancer J Clin"},{"key":"B32","doi-asserted-by":"publisher","first-page":"e13","DOI":"10.1016\/j.clbc.2014.05.006","article-title":"Association between ligands and receptors related to the progression of early breast cancer in tumor epithelial and stromal cells","volume":"15","author":"Labovsky","year":"2015","journal-title":"Clin Br Cancer"},{"key":"B33","doi-asserted-by":"publisher","first-page":"280","DOI":"10.1186\/s12885-017-3259-8","article-title":"Prognostic significance of TRAIL-R3 and CCR-2 expression in tumor epithelial cells of patients with early breast cancer","volume":"17","author":"Labovsky","year":"2017","journal-title":"BMC Cancer"},{"key":"B34","doi-asserted-by":"publisher","first-page":"2057","DOI":"10.3892\/or.2017.5449","article-title":"Dysregulation of TMPRSS3 and TNFRSF11B correlates with tumorigenesis and poor prognosis in patients with breast cancer","volume":"37","author":"Luo","year":"2017","journal-title":"Oncol Rep"},{"key":"B35","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1007\/s10549-017-4318-1","article-title":"Receptor activator of nuclear factor kappa B (RANK) expression in primary breast cancer correlates with recurrence-free survival and development of bone metastases in I-SPY1 (CALGB 150007\/15 ACRIN 6657)","volume":"165","author":"Vidula","year":"2017","journal-title":"Br Cancer Res Treat"},{"key":"B36","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1016\/j.tranon.2017.05.006","article-title":"Evaluation of the prognostic value of RANK, OPG, and RANKL mRNA expression in early breast cancer patients treated with anthracycline-based adjuvant chemotherapy","volume":"10","author":"Timotheadou","year":"2017","journal-title":"Transl Oncol"},{"key":"B37","doi-asserted-by":"publisher","first-page":"1369","DOI":"10.1158\/1078-0432.CCR-18-2482","article-title":"Prognostic value of RANKL\/OPG serum levels and disseminated tumor cells in nonmetastatic breast cancer","volume":"25","author":"Rachner","year":"2019","journal-title":"Clin Cancer Res"},{"key":"B38","doi-asserted-by":"publisher","first-page":"1112","DOI":"10.1002\/cam4.277","article-title":"Osteoprotegerin expression in triple-negative breast cancer cells promotes metastasis","volume":"3","author":"Weichhaus","year":"2014","journal-title":"Cancer Med"},{"key":"B39","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1186\/s12943-017-0606-y","article-title":"Osteoprotegerin mediates tumor-promoting effects of Interleukin-1beta in breast cancer cells","volume":"16","author":"Chung","year":"2017","journal-title":"Mol Cancer"},{"key":"B40","doi-asserted-by":"publisher","first-page":"736","DOI":"10.1016\/j.bbrc.2008.01.118","article-title":"17beta-Estradiol inhibits osteoprotegerin production by the estrogen receptor-alpha-positive human breast cancer cell line MCF-7","volume":"368","author":"Rachner","year":"2008","journal-title":"Biochem Biophys Res Commun"},{"key":"B41","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/j.ctrv.2017.10.010","article-title":"The anti-tumor effect of RANKL inhibition in malignant solid tumors - A systematic review","volume":"62","author":"de Groot","year":"2018","journal-title":"Cancer Treat Rev"},{"key":"B42","doi-asserted-by":"publisher","first-page":"5857","DOI":"10.1158\/0008-5472.CAN-15-2745","article-title":"RANK signaling blockade reduces breast cancer recurrence by inducing tumor cell differentiation","volume":"76","author":"Yoldi","year":"2016","journal-title":"Cancer Res"},{"key":"B43","doi-asserted-by":"publisher","first-page":"935","DOI":"10.1186\/s12885-015-1837-1","article-title":"Osteoprotegerin secreted by inflammatory and invasive breast cancer cells induces aneuploidy, cell proliferation and angiogenesis","volume":"15","author":"Goswami","year":"2015","journal-title":"BMC Cancer"},{"key":"B44","doi-asserted-by":"publisher","first-page":"968","DOI":"10.1002\/ijc.29439","article-title":"OPG-Fc inhibits ovariectomy-induced growth of disseminated breast cancer cells in bone","volume":"137","author":"Ottewell","year":"2015","journal-title":"Int J Cancer"},{"key":"B45","doi-asserted-by":"publisher","first-page":"532","DOI":"10.3892\/ijo.2014.2468","article-title":"Pharmacologic inhibition of bone resorption prevents cancer-induced osteolysis but enhances soft tissue metastasis in a mouse model of osteolytic breast cancer","volume":"45","author":"Zinonos","year":"2014","journal-title":"Int J Oncol"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fonc.2020.00462\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,4,7]],"date-time":"2020-04-07T04:36:54Z","timestamp":1586234214000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fonc.2020.00462\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4,7]]},"references-count":45,"alternative-id":["10.3389\/fonc.2020.00462"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2020.00462","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,4,7]]},"article-number":"462"}}