{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T15:33:21Z","timestamp":1793806401894,"version":"4.6.1"},"reference-count":34,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,9,12]],"date-time":"2017-09-12T00:00:00Z","timestamp":1505174400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,9,12]],"date-time":"2017-09-12T00:00:00Z","timestamp":1505174400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Breast cancer is the second leading cause of cancer-related deaths among women worldwide. Many patients suffer from bone metastasis. Sclerostin, a key regulator of normal bone remodeling, is critically involved in osteolytic bone diseases. However, its role in breast cancer bone metastasis remains unknown. Here, we found that sclerostin was overexpressed in breast cancer tumor tissues and cell lines. Inhibition of sclerostin by antibody (Scl-Ab) significantly reduced migration and invasion of MDA-MB-231 and MCF-7 cells in a time- and dose-dependent manner. In xenograft model, sclerostin inhibition improved survival of nude mice and prevented osteolytic lesions resulting from tumor metastasis. Taken together, sclerostin promotes breast cancer cell migration, invasion and bone osteolysis. Inhibition of sclerostin may serve as an efficient strategy for interventions against breast cancer bone metastasis or osteolytic bone diseases.<\/jats:p>","DOI":"10.1038\/s41598-017-11913-7","type":"journal-article","created":{"date-parts":[[2017,9,6]],"date-time":"2017-09-06T22:16:25Z","timestamp":1504736185000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Sclerostin induced tumor growth, bone metastasis and osteolysis in breast cancer"],"prefix":"10.1038","volume":"7","author":[{"given":"Menghai","family":"Zhu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changzhen","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shifei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shudong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingkun","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,9,12]]},"reference":[{"key":"11913_CR1","doi-asserted-by":"publisher","first-page":"212","DOI":"10.3322\/caac.20121","volume":"61","author":"R Siegel","year":"2011","unstructured":"Siegel, R., Ward, E., Brawley, O. & Jemal, A. Cancer statistics, 2011: the impact of eliminating socioeconomic and racial disparities on premature cancer deaths. CA: a cancer journal for clinicians \n                           61, 212\u2013236, https:\/\/doi.org\/10.3322\/caac.20121 (2011).","journal-title":"CA: a cancer journal for clinicians"},{"key":"11913_CR2","doi-asserted-by":"publisher","first-page":"69","DOI":"10.3322\/caac.20107","volume":"61","author":"A Jemal","year":"2011","unstructured":"Jemal, A. et al. Global cancer statistics. CA: a cancer journal for clinicians \n                           61, 69\u201390, https:\/\/doi.org\/10.3322\/caac.20107 (2011).","journal-title":"CA: a cancer journal for clinicians"},{"key":"11913_CR3","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1007\/s10549-011-1721-x","volume":"131","author":"N Sathiakumar","year":"2012","unstructured":"Sathiakumar, N. et al. Mortality following bone metastasis and skeletal-related events among women with breast cancer: a population-based analysis of U.S. Medicare beneficiaries, 1999-2006. Breast cancer research and treatment \n                           131, 231\u2013238, https:\/\/doi.org\/10.1007\/s10549-011-1721-x (2012).","journal-title":"Breast cancer research and treatment"},{"key":"11913_CR4","doi-asserted-by":"publisher","first-page":"587","DOI":"10.1200\/JCO.2010.33.5232","volume":"30","author":"E Amir","year":"2012","unstructured":"Amir, E. et al. Prospective study evaluating the impact of tissue confirmation of metastatic disease in patients with breast cancer. Journal of clinical oncology: official journal of the American Society of Clinical Oncology \n                           30, 587\u2013592, https:\/\/doi.org\/10.1200\/JCO.2010.33.5232 (2012).","journal-title":"Journal of clinical oncology: official journal of the American Society of Clinical Oncology"},{"key":"11913_CR5","doi-asserted-by":"publisher","first-page":"3279","DOI":"10.1007\/s00520-013-1887-3","volume":"21","author":"G Oster","year":"2013","unstructured":"Oster, G. et al. Natural history of skeletal-related events in patients with breast, lung, or prostate cancer and metastases to bone: a 15-year study in two large US health systems. Supportive care in cancer: official journal of the Multinational Association of Supportive Care in Cancer \n                           21, 3279\u20133286, https:\/\/doi.org\/10.1007\/s00520-013-1887-3 (2013).","journal-title":"Supportive care in cancer: official journal of the Multinational Association of Supportive Care in Cancer"},{"key":"11913_CR6","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0062295","volume":"8","author":"M van Dinther","year":"2013","unstructured":"van Dinther, M. et al. Anti-Sclerostin antibody inhibits internalization of Sclerostin and Sclerostin-mediated antagonism of Wnt\/LRP6 signaling. PloS one \n                           8, e62295, https:\/\/doi.org\/10.1371\/journal.pone.0062295 (2013).","journal-title":"PloS one"},{"key":"11913_CR7","doi-asserted-by":"publisher","unstructured":"Qin, W. et al. Mice with sclerostin gene deletion are resistant to the severe sublesional bone loss induced by spinal cord injury. Osteoporosis international: a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA, https:\/\/doi.org\/10.1007\/s00198-016-3700-x (2016).","DOI":"10.1007\/s00198-016-3700-x"},{"key":"11913_CR8","doi-asserted-by":"publisher","first-page":"1225","DOI":"10.1002\/jbmr.2789","volume":"31","author":"H Eda","year":"2016","unstructured":"Eda, H. et al. Regulation of Sclerostin Expression in Multiple Myeloma by Dkk-1: A Potential Therapeutic Strategy for Myeloma Bone Disease. Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research \n                           31, 1225\u20131234, https:\/\/doi.org\/10.1002\/jbmr.2789 (2016).","journal-title":"Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research"},{"key":"11913_CR9","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1016\/j.leukres.2014.02.010","volume":"38","author":"XT Wang","year":"2014","unstructured":"Wang, X. T. et al. Bone marrow plasma macrophage inflammatory protein protein-1 alpha(MIP-1 alpha) and sclerostin in multiple myeloma: relationship with bone disease and clinical characteristics. Leukemia research \n                           38, 525\u2013531, https:\/\/doi.org\/10.1016\/j.leukres.2014.02.010 (2014).","journal-title":"Leukemia research"},{"key":"11913_CR10","doi-asserted-by":"publisher","DOI":"10.1038\/bcj.2011.22","volume":"1","author":"S Colucci","year":"2011","unstructured":"Colucci, S. et al. Myeloma cells suppress osteoblasts through sclerostin secretion. Blood cancer journal \n                           1, e27, https:\/\/doi.org\/10.1038\/bcj.2011.22 (2011).","journal-title":"Blood cancer journal"},{"key":"11913_CR11","doi-asserted-by":"publisher","first-page":"1466","DOI":"10.1002\/ijc.27342","volume":"131","author":"E Terpos","year":"2012","unstructured":"Terpos, E. et al. Elevated circulating sclerostin correlates with advanced disease features and abnormal bone remodeling in symptomatic myeloma: reduction post-bortezomib monotherapy. 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Advanced drug delivery reviews \n                           99, 206\u2013211, https:\/\/doi.org\/10.1016\/j.addr.2015.11.017 (2016).","journal-title":"Advanced drug delivery reviews"},{"key":"11913_CR16","doi-asserted-by":"publisher","first-page":"2370","DOI":"10.1038\/onc.2015.297","volume":"35","author":"X Meng","year":"2016","unstructured":"Meng, X. et al. Myeloid-specific TGF-beta signaling in bone promotes basic-FGF and breast cancer bone metastasis. Oncogene \n                           35, 2370\u20132378, https:\/\/doi.org\/10.1038\/onc.2015.297 (2016).","journal-title":"Oncogene"},{"key":"11913_CR17","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1007\/s00441-014-1846-4","volume":"357","author":"M Yamaguchi","year":"2014","unstructured":"Yamaguchi, M. et al. Curcumin analogue UBS109 prevents bone loss in breast cancer bone metastasis mouse model: involvement in osteoblastogenesis and osteoclastogenesis. Cell and tissue research \n                           357, 245\u2013252, https:\/\/doi.org\/10.1007\/s00441-014-1846-4 (2014).","journal-title":"Cell and tissue research"},{"key":"11913_CR18","doi-asserted-by":"publisher","first-page":"672","DOI":"10.1158\/0008-5472.CAN-12-2202","volume":"73","author":"A Sawant","year":"2013","unstructured":"Sawant, A. et al. Myeloid-derived suppressor cells function as novel osteoclast progenitors enhancing bone loss in breast cancer. Cancer research \n                           73, 672\u2013682, https:\/\/doi.org\/10.1158\/0008-5472.CAN-12-2202 (2013).","journal-title":"Cancer research"},{"key":"11913_CR19","doi-asserted-by":"publisher","first-page":"2737","DOI":"10.1038\/onc.2013.238","volume":"33","author":"J Huang","year":"2014","unstructured":"Huang, J. et al. EphA2 promotes epithelial-mesenchymal transition through the Wnt\/beta-catenin pathway in gastric cancer cells. 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Journal of biological regulators and homeostatic agents \n                           30, 399\u2013408 (2016).","journal-title":"Journal of biological regulators and homeostatic agents"},{"key":"11913_CR24","doi-asserted-by":"publisher","first-page":"1671","DOI":"10.1007\/s00432-014-1726-z","volume":"140","author":"I Kyvernitakis","year":"2014","unstructured":"Kyvernitakis, I. et al. Effect of aromatase inhibition on serum levels of sclerostin and dickkopf-1, bone turnover markers and bone mineral density in women with breast cancer. Journal of cancer research and clinical oncology \n                           140, 1671\u20131680, https:\/\/doi.org\/10.1007\/s00432-014-1726-z (2014).","journal-title":"Journal of cancer research and clinical oncology"},{"key":"11913_CR25","first-page":"348","volume":"7","author":"CP Geffre","year":"2015","unstructured":"Geffre, C. P. et al. Combined micro CT and histopathology for evaluation of skeletal metastasis in live animals. American journal of translational research \n                           7, 348\u2013355 (2015).","journal-title":"American journal of translational research"},{"key":"11913_CR26","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0079101","volume":"8","author":"S Previdi","year":"2013","unstructured":"Previdi, S. et al. Combination of the c-Met inhibitor tivantinib and zoledronic acid prevents tumor bone engraftment and inhibits progression of established bone metastases in a breast xenograft model. PloS one \n                           8, e79101, https:\/\/doi.org\/10.1371\/journal.pone.0079101 (2013).","journal-title":"PloS one"},{"key":"11913_CR27","doi-asserted-by":"publisher","unstructured":"Florio,M. et al. A bispecific antibody targeting sclerostin and DKK-1 promotes bone mass accrual and fracture repair. NATURE COMMUNICATIONS 7, doi:https:\/\/doi.org\/10.1038\/ncomms11505.2015.09.029 (2016).","DOI":"10.1038\/ncomms11505.2015.09.029"},{"key":"11913_CR28","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1016\/j.bone.2012.09.029","volume":"52","author":"R Zhang","year":"2013","unstructured":"Zhang, R. et al. Wnt\/beta-catenin signaling activates bone morphogenetic protein 2 expression in osteoblasts. Bone \n                           52, 145\u2013156, https:\/\/doi.org\/10.1016\/j.bone.2012.09.029 (2013).","journal-title":"Bone"},{"key":"11913_CR29","doi-asserted-by":"publisher","first-page":"274","DOI":"10.1016\/j.arcmed.2012.06.002","volume":"43","author":"J Zhou","year":"2012","unstructured":"Zhou, J. et al. Effects of pulsed electromagnetic fields on bone mass and Wnt\/beta-catenin signaling pathway in ovariectomized rats. Archives of medical research \n                           43, 274\u2013282, https:\/\/doi.org\/10.1016\/j.arcmed.2012.06.002 (2012).","journal-title":"Archives of medical research"},{"key":"11913_CR30","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1016\/j.bone.2015.03.019","volume":"76","author":"N Lara-Castillo","year":"2015","unstructured":"Lara-Castillo, N. et al. In vivo mechanical loading rapidly activates beta-catenin signaling in osteocytes through a prostaglandin mediated mechanism. Bone \n                           76, 58\u201366, https:\/\/doi.org\/10.1016\/j.bone.2015.03.019 (2015).","journal-title":"Bone"},{"key":"11913_CR31","doi-asserted-by":"publisher","first-page":"1196","DOI":"10.1002\/jbmr.2147","volume":"29","author":"M Zahoor","year":"2014","unstructured":"Zahoor, M., Cha, P. H., Min do, S. & Choi, K. Y. Indirubin-3\u2032-oxime reverses bone loss in ovariectomized and hindlimb-unloaded mice via activation of the Wnt\/beta-catenin signaling. Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research \n                           29, 1196\u20131205, https:\/\/doi.org\/10.1002\/jbmr.2147 (2014).","journal-title":"Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research"},{"key":"11913_CR32","doi-asserted-by":"publisher","first-page":"855","DOI":"10.1007\/s40618-015-0421-5","volume":"39","author":"P Wanby","year":"2016","unstructured":"Wanby, P., Nobin, R., Von, S. P., Brudin, L. & Carlsson, M. Serum levels of the bone turnover markers dickkopf-1, sclerostin, osteoprotegerin, osteopontin, osteocalcin and 25-hydroxyvitamin D in Swedish geriatric patients aged 75 years or older with a fresh hip fracture and in healthy controls. Journal of endocrinological investigation \n                           39, 855\u2013863, https:\/\/doi.org\/10.1007\/s40618-015-0421-5 (2016).","journal-title":"Journal of endocrinological investigation"},{"key":"11913_CR33","doi-asserted-by":"publisher","first-page":"E587","DOI":"10.1152\/ajpendo.00219.2016","volume":"311","author":"M Piemontese","year":"2016","unstructured":"Piemontese, M., Xiong, J., Fujiwara, Y., Thostenson, J. D. & O\u2019Brien, C. A. Cortical bone loss caused by glucocorticoid excess requires RANKL production by osteocytes and is associated with reduced OPG expression in mice. American journal of physiology. Endocrinology and metabolism \n                           311, E587\u2013593, https:\/\/doi.org\/10.1152\/ajpendo.00219.2016 (2016).","journal-title":"American journal of physiology. 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