{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T03:16:14Z","timestamp":1785294974366,"version":"3.55.0"},"reference-count":40,"publisher":"Springer Science and Business Media LLC","issue":"1","funder":[{"DOI":"10.13039\/501100000289","name":"Cancer Research UK (GB)","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Exp Clin Cancer Res"],"published-print":{"date-parts":[[2015,12]]},"DOI":"10.1186\/s13046-015-0240-8","type":"journal-article","created":{"date-parts":[[2015,10,20]],"date-time":"2015-10-20T12:01:41Z","timestamp":1445342501000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["The frequency of osteolytic bone metastasis is determined by conditions of the soil, not the number of seeds; evidence from in vivo models of breast and prostate cancer"],"prefix":"10.1186","volume":"34","author":[{"given":"Ning","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberley J.","family":"Reeves","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah K.","family":"Brown","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne C M","family":"Fowles","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Freyja E.","family":"Docherty","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Penelope D.","family":"Ottewell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter I.","family":"Croucher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingunn","family":"Holen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colby L.","family":"Eaton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2015,10,20]]},"reference":[{"issue":"6","key":"240_CR1","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1186\/bcr2781","volume":"12","author":"YC Chen","year":"2010","unstructured":"Chen YC, Sosnoski DM, Mastro AM. Breast cancer metastasis to the bone: mechanisms of bone loss. Breast Cancer Res. 2010;12(6):215.","journal-title":"Breast Cancer Res"},{"issue":"5","key":"240_CR2","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1053\/hp.2000.6698","volume":"31","author":"L Bubendorf","year":"2000","unstructured":"Bubendorf L, Schopfer A, Wagner U, Sauter G, Moch H, Willi N, et al. Metastatic patterns of prostate cancer: an autopsy study of 1,589 patients. Hum Pathol. 2000;31(5):578\u201383.","journal-title":"Hum Pathol"},{"key":"240_CR3","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/s13046-015-0122-0","volume":"34","author":"M Santoni","year":"2015","unstructured":"Santoni M, Conti A, Procopio G, Porta C, Ibrahim T, Barni S, et al. Bone metastases in patients with metastatic renal cell carcinoma: are they always associated with poor prognosis? J Exp Clin Cancer Res. 2015;34:10.","journal-title":"J Exp Clin Cancer Res"},{"issue":"3","key":"240_CR4","first-page":"307","volume":"26","author":"G Facchini","year":"2007","unstructured":"Facchini G, Caraglia M, Santini D, Nasti G, Ottaiano A, Striano S, et al. The clinical response on bone metastasis from breast and lung cancer during treatment with zoledronic acid is inversely correlated to skeletal related events (SRE). J Exp Clin Cancer Res. 2007;26(3):307\u201312.","journal-title":"J Exp Clin Cancer Res"},{"issue":"15","key":"240_CR5","doi-asserted-by":"crossref","first-page":"1396","DOI":"10.1056\/NEJMoa1105195","volume":"365","author":"RE Coleman","year":"2011","unstructured":"Coleman RE, Marshall H, Cameron D, Dodwell D, Burkinshaw R, Keane M, et al. Breast-cancer adjuvant therapy with zoledronic acid. N Engl J Med. 2011;365(15):1396\u2013405.","journal-title":"N Engl J Med"},{"issue":"7","key":"240_CR6","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1016\/S1470-2045(11)70122-X","volume":"12","author":"M Gnant","year":"2011","unstructured":"Gnant M, Mlineritsch B, Stoeger H, Luschin-Ebengreuth G, Heck D, Menzel C, et al. Adjuvant endocrine therapy plus zoledronic acid in premenopausal women with early-stage breast cancer: 62-month follow-up from the ABCSG-12 randomised trial. Lancet Oncol. 2011;12(7):631\u201341.","journal-title":"Lancet Oncol"},{"issue":"1","key":"240_CR7","doi-asserted-by":"crossref","first-page":"261","DOI":"10.2147\/TCRM.S2707","volume":"4","author":"TJ Polascik","year":"2008","unstructured":"Polascik TJ, Mouraviev V. Zoledronic acid in the management of metastatic bone disease. Ther Clin Risk Manag. 2008;4(1):261\u20138.","journal-title":"Ther Clin Risk Manag"},{"issue":"2","key":"240_CR8","first-page":"98","volume":"8","author":"S Paget","year":"1989","unstructured":"Paget S. The distribution of secondary growths in cancer of the breast. 1889. Cancer Metastasis Rev. 1989;8(2):98\u2013101.","journal-title":"Cancer Metastasis Rev"},{"issue":"23","key":"240_CR9","doi-asserted-by":"crossref","first-page":"10946","DOI":"10.1158\/0008-5472.CAN-05-2018","volume":"65","author":"AT Collins","year":"2005","unstructured":"Collins AT, Berry PA, Hyde C, Stower MJ, Maitland NJ. Prospective identification of tumorigenic prostate cancer stem cells. Cancer Res. 2005;65(23):10946\u201351.","journal-title":"Cancer Res"},{"issue":"7","key":"240_CR10","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1002\/pros.21473","volume":"72","author":"M Colombel","year":"2012","unstructured":"Colombel M, Eaton CL, Hamdy F, Ricci E, van der Pluijm G, Cecchini M, et al. Increased expression of putative cancer stem cell markers in primary prostate cancer is associated with progression of bone metastases. Prostate. 2012;72(7):713\u201320.","journal-title":"Prostate"},{"issue":"8","key":"240_CR11","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1002\/pros.21121","volume":"70","author":"CL Eaton","year":"2010","unstructured":"Eaton CL, Colombel M, van der Pluijm G, Cecchini M, Wetterwald A, Lippitt J, et al. Evaluation of the frequency of putative prostate cancer stem cells in primary and metastatic prostate cancer. Prostate. 2010;70(8):875\u201382.","journal-title":"Prostate"},{"issue":"42","key":"240_CR12","doi-asserted-by":"crossref","first-page":"18115","DOI":"10.1073\/pnas.1006732107","volume":"107","author":"H Liu","year":"2010","unstructured":"Liu H, Patel MR, Prescher JA, Patsialou A, Qian D, Lin J, et al. Cancer stem cells from human breast tumors are involved in spontaneous metastases in orthotopic mouse models. Proc Natl Acad Sci U S A. 2010;107(42):18115\u201320.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"7","key":"240_CR13","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1038\/modpathol.2012.37","volume":"25","author":"G Guler","year":"2012","unstructured":"Guler G, Balci S, Costinean S, Ussakli CH, Irkkan C, Suren D, et al. Stem cell-related markers in primary breast cancers and associated metastatic lesions. Mod Pathol. 2012;25(7):949\u201355.","journal-title":"Mod Pathol"},{"issue":"6","key":"240_CR14","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1593\/neo.11122","volume":"13","author":"G Horst van der","year":"2011","unstructured":"van der Horst G, van den Hoogen C, Buijs JT, Cheung H, Bloys H, Pelger RC, et al. Targeting of alpha(v)-integrins in stem\/progenitor cells and supportive microenvironment impairs bone metastasis in human prostate cancer. Neoplasia. 2011;13(6):516\u201325.","journal-title":"Neoplasia"},{"issue":"2","key":"240_CR15","doi-asserted-by":"crossref","first-page":"2688","DOI":"10.1002\/jbmr.2300","volume":"29","author":"N Wang","year":"2014","unstructured":"Wang N, Docherty FE, Brown HK, Reeves KJ, Fowles AC, Ottewell PD, et al. Prostate cancer cells preferentially home to osteoblast-rich areas in the early stages of bone metastasis - evidence from in vivo models. J Bone Miner Res. 2014;29(2):2688\u201396.","journal-title":"J Bone Miner Res"},{"issue":"4","key":"240_CR16","doi-asserted-by":"crossref","first-page":"1298","DOI":"10.1172\/JCI43414","volume":"121","author":"Y Shiozawa","year":"2011","unstructured":"Shiozawa Y, Pedersen EA, Havens AM, Jung Y, Mishra A, Joseph J, et al. Human prostate cancer metastases target the hematopoietic stem cell niche to establish footholds in mouse bone marrow. J Clin Invest. 2011;121(4):1298\u2013312.","journal-title":"J Clin Invest"},{"issue":"5","key":"240_CR17","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1530\/ERC-14-0199","volume":"21","author":"PD Ottewell","year":"2014","unstructured":"Ottewell PD, Wang N, Meek J, Fowles CA, Croucher PI, Eaton CL, et al. Castration-induced bone loss triggers growth of disseminated prostate cancer cells in bone. Endocr Relat Cancer. 2014;21(5):769\u201381.","journal-title":"Endocr Relat Cancer"},{"issue":"11","key":"240_CR18","doi-asserted-by":"crossref","first-page":"2922","DOI":"10.1158\/1078-0432.CCR-13-1246","volume":"20","author":"PD Ottewell","year":"2014","unstructured":"Ottewell PD, Wang N, Brown HK, Reeves KJ, Fowles CA, Croucher PI, et al. Zoledronic acid has differential antitumor activity in the pre- and postmenopausal bone microenvironment in vivo. Clin Cancer Res. 2014;20(11):2922\u201332.","journal-title":"Clin Cancer Res"},{"issue":"9810","key":"240_CR19","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/S0140-6736(11)61226-9","volume":"379","author":"MR Smith","year":"2012","unstructured":"Smith MR, Saad F, Coleman R, Shore N, Fizazi K, Tombal B, et al. Denosumab and bone-metastasis-free survival in men with castration-resistant prostate cancer: results of a phase 3, randomised, placebo-controlled trial. Lancet. 2012;379(9810):39\u201346.","journal-title":"Lancet"},{"issue":"27","key":"240_CR20","doi-asserted-by":"crossref","first-page":"3605","DOI":"10.1200\/JCO.2010.31.5069","volume":"29","author":"A Lipton","year":"2011","unstructured":"Lipton A, Chapman JA, Demers L, Shepherd LE, Han L, Wilson CF, et al. Elevated bone turnover predicts for bone metastasis in postmenopausal breast cancer: results of NCIC CTG MA.14. J Clin Oncol. 2011;29(27):3605\u201310.","journal-title":"J Clin Oncol"},{"issue":"35","key":"240_CR21","doi-asserted-by":"crossref","first-page":"5132","DOI":"10.1200\/JCO.2010.29.7101","volume":"28","author":"AT Stopeck","year":"2010","unstructured":"Stopeck AT, Lipton A, Body JJ, Steger GG, Tonkin K, de Boer RH, et al. Denosumab compared with zoledronic acid for the treatment of bone metastases in patients with advanced breast cancer: a randomized, double-blind study. J Clin Oncol. 2010;28(35):5132\u20139.","journal-title":"J Clin Oncol"},{"issue":"9768","key":"240_CR22","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1016\/S0140-6736(10)62344-6","volume":"377","author":"K Fizazi","year":"2011","unstructured":"Fizazi K, Carducci M, Smith M, Damiao R, Brown J, Karsh L, et al. Denosumab versus zoledronic acid for treatment of bone metastases in men with castration-resistant prostate cancer: a randomised, double-blind study. Lancet. 2011;377(9768):813\u201322.","journal-title":"Lancet"},{"issue":"6","key":"240_CR23","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1002\/cyto.a.22434","volume":"85","author":"K Yumoto","year":"2014","unstructured":"Yumoto K, Berry JE, Taichman RS, Shiozawa Y. A novel method for monitoring tumor proliferation in vivo using fluorescent dye DiD. Cytometry A. 2014;85(6):548\u201355.","journal-title":"Cytometry A"},{"issue":"8","key":"240_CR24","doi-asserted-by":"crossref","first-page":"3141","DOI":"10.1096\/fj.14-266379","volume":"29","author":"N Wang","year":"2015","unstructured":"Wang N, Docherty F, Brown HK, Reeves K, Fowles A, Lawson M, et al. Mitotic quiescence, but not unique \"stemness,\" marks the phenotype of bone metastasis-initiating cells in prostate cancer. FASEB J. 2015;29(8):3141\u201350.","journal-title":"FASEB J"},{"issue":"7","key":"240_CR25","doi-asserted-by":"crossref","first-page":"1468","DOI":"10.1002\/jbmr.141","volume":"25","author":"ML Bouxsein","year":"2010","unstructured":"Bouxsein ML, Boyd SK, Christiansen BA, Guldberg RE, Jepsen KJ, Muller R. Guidelines for assessment of bone microstructure in rodents using micro-computed tomography. J Bone Miner Res. 2010;25(7):1468\u201386.","journal-title":"J Bone Miner Res"},{"issue":"1","key":"240_CR26","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1210\/me.2011-1083","volume":"26","author":"N Wang","year":"2012","unstructured":"Wang N, Robaye B, Agrawal A, Skerry TM, Boeynaems JM, Gartland A. Reduced bone turnover in mice lacking the P2Y(13) receptor of ADP. Mol Endocrinol. 2012;26(1):142\u201352.","journal-title":"Mol Endocrinol"},{"issue":"3","key":"240_CR27","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1016\/S0002-9440(10)64934-6","volume":"160","author":"A Wetterwald","year":"2002","unstructured":"Wetterwald A, van der Pluijm G, Que I, Sijmons B, Buijs J, Karperien M, et al. Optical imaging of cancer metastasis to bone marrow: a mouse model of minimal residual disease. Am J Pathol. 2002;160(3):1143\u201353.","journal-title":"Am J Pathol"},{"issue":"22","key":"240_CR28","doi-asserted-by":"crossref","first-page":"4821","DOI":"10.1200\/JCO.2005.02.911","volume":"23","author":"GD Roodman","year":"2005","unstructured":"Roodman GD. High bone turnover markers predict poor outcome in patients with bone metastasis. J Clin Oncol. 2005;23(22):4821\u20132.","journal-title":"J Clin Oncol"},{"issue":"12","key":"240_CR29","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.1243\/09544119JEIM821","volume":"224","author":"P Jayakumar","year":"2010","unstructured":"Jayakumar P, Di Silvio L. Osteoblasts in bone tissue engineering. Proc Inst Mech Eng H. 2010;224(12):1415\u201340.","journal-title":"Proc Inst Mech Eng H"},{"issue":"2","key":"240_CR30","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1016\/j.bone.2006.09.016","volume":"40","author":"Y Zheng","year":"2007","unstructured":"Zheng Y, Zhou H, Brennan K, Blair JM, Modzelewski JR, Seibel MJ, et al. Inhibition of bone resorption, rather than direct cytotoxicity, mediates the anti-tumour actions of ibandronate and osteoprotegerin in a murine model of breast cancer bone metastasis. Bone. 2007;40(2):471\u20138.","journal-title":"Bone"},{"issue":"10","key":"240_CR31","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.1172\/JCI11685","volume":"107","author":"J Zhang","year":"2001","unstructured":"Zhang J, Dai J, Qi Y, Lin DL, Smith P, Strayhorn C, et al. Osteoprotegerin inhibits prostate cancer-induced osteoclastogenesis and prevents prostate tumor growth in the bone. J Clin Invest. 2001;107(10):1235\u201344.","journal-title":"J Clin Invest"},{"issue":"4","key":"240_CR32","doi-asserted-by":"crossref","first-page":"1727","DOI":"10.1210\/en.2004-1211","volume":"146","author":"A Schneider","year":"2005","unstructured":"Schneider A, Kalikin LM, Mattos AC, Keller ET, Allen MJ, Pienta KJ, et al. Bone turnover mediates preferential localization of prostate cancer in the skeleton. Endocrinology. 2005;146(4):1727\u201336.","journal-title":"Endocrinology"},{"issue":"3","key":"240_CR33","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1053\/j.seminoncol.2009.03.001","volume":"36","author":"CK Anders","year":"2009","unstructured":"Anders CK, Johnson R, Litton J, Phillips M, Bleyer A. Breast cancer before age 40 years. Semin Oncol. 2009;36(3):237\u201349.","journal-title":"Semin Oncol"},{"issue":"13","key":"240_CR34","doi-asserted-by":"crossref","first-page":"2863","DOI":"10.1002\/cncr.24324","volume":"115","author":"DW Lin","year":"2009","unstructured":"Lin DW, Porter M, Montgomery B. Treatment and survival outcomes in young men diagnosed with prostate cancer: a Population-based Cohort Study. Cancer. 2009;115(13):2863\u201371.","journal-title":"Cancer"},{"key":"240_CR35","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1038\/bonekey.2014.95","volume":"3","author":"AH Capietto","year":"2014","unstructured":"Capietto AH, Faccio R. Immune regulation of bone metastasis. Bonekey Rep. 2014;3:600.","journal-title":"Bonekey Rep"},{"issue":"1","key":"240_CR36","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1007\/s10555-007-9109-4","volume":"27","author":"KM Bussard","year":"2008","unstructured":"Bussard KM, Gay CV, Mastro AM. The bone microenvironment in metastasis; what is special about bone? Cancer Metastasis Rev. 2008;27(1):41\u201355.","journal-title":"Cancer Metastasis Rev"},{"issue":"7044","key":"240_CR37","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1038\/nature03703","volume":"435","author":"DA Sipkins","year":"2005","unstructured":"Sipkins DA, Wei X, Wu JW, Runnels JM, Cote D, Means TK, et al. In vivo imaging of specialized bone marrow endothelial microdomains for tumour engraftment. Nature. 2005;435(7044):969\u201373.","journal-title":"Nature"},{"issue":"20","key":"240_CR38","doi-asserted-by":"crossref","first-page":"5281","DOI":"10.1182\/blood-2011-01-315069","volume":"117","author":"P Bianco","year":"2011","unstructured":"Bianco P. Bone and the hematopoietic niche: a tale of two stem cells. Blood. 2011;117(20):5281\u20138.","journal-title":"Blood"},{"issue":"7492","key":"240_CR39","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1038\/nature13145","volume":"507","author":"AP Kusumbe","year":"2014","unstructured":"Kusumbe AP, Ramasamy SK, Adams RH. Coupling of angiogenesis and osteogenesis by a specific vessel subtype in bone. Nature. 2014;507(7492):323\u20138.","journal-title":"Nature"},{"issue":"1","key":"240_CR40","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1038\/cr.2008.316","volume":"19","author":"D Padua","year":"2009","unstructured":"Padua D, Massague J. Roles of TGFbeta in metastasis. Cell Res. 2009;19(1):89\u2013102.","journal-title":"Cell Res"}],"container-title":["Journal of Experimental & Clinical Cancer Research"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13046-015-0240-8","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,9,10]],"date-time":"2020-09-10T00:35:21Z","timestamp":1599698121000},"score":1,"resource":{"primary":{"URL":"http:\/\/jeccr.biomedcentral.com\/articles\/10.1186\/s13046-015-0240-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,10,20]]},"references-count":40,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2015,12]]}},"alternative-id":["240"],"URL":"https:\/\/doi.org\/10.1186\/s13046-015-0240-8","relation":{},"ISSN":["1756-9966"],"issn-type":[{"value":"1756-9966","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,10,20]]},"article-number":"124"}}