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A unique in vitro 3D tumor model that uses a sequential culture (SC) of human mesenchymal stem cells followed by seeding with cancer cells after bone formation was initiated to study the phenotype\u2010specific interaction between prostate cancer cells and bone microenvironment. The PCa cells were observed to be less prolific and less metastatic, and to form multicellular tumoroids in the bone microenvironment, whereas PC\u20103 cells were more prolific and were highly metastatic, and did not form multicellular tumoroids in the bone microenvironment. The metastatic process exhibited by these two prostate cancer cell lines showed a significant and different effect on bone mineralization and extracellular matrix formation. Excessive bone formation in the presence of PC\u20103 and significant osteolysis in the presence of PCa were observed, which was also indicated by osteocalcin and MMP\u20109 expression as measured by ELISA and qRT\u2010PCR. The field emission scanning electron microscopy images revealed that the structure of mineralized collagen in the presence of PC\u20103 is different than the one observed in healthy bone. All experimental results indicated that both osteolytic and osteoblastic bone lesions can be recapitulated in our tumor testbed model and that different cancer phenotypes have a very different influence on bone at metastasis. The 3D in vitro model presented in this study provides an improved, reproducible, and controllable system that is a useful tool to elucidate osteotropism of prostate cancer cells. \u00a9 2019 The Authors. <jats:italic>JBMR Plus<\/jats:italic> published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.<\/jats:p>","DOI":"10.1002\/jbm4.10256","type":"journal-article","created":{"date-parts":[[2019,11,19]],"date-time":"2019-11-19T17:48:13Z","timestamp":1574185693000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Prostate Cancer Phenotype Influences Bone Mineralization at Metastasis: A Study Using an In Vitro Prostate Cancer Metastasis Testbed"],"prefix":"10.1093","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3643-2385","authenticated-orcid":false,"given":"MD Shahjahan","family":"Molla","sequence":"first","affiliation":[{"name":"Center for Engineered Cancer Testbeds North Dakota State University  Fargo ND USA"},{"name":"Department of Civil and Environmental Engineering North Dakota State University  Fargo ND USA"},{"name":"Scintillon Institute San Diego  USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9866-2683","authenticated-orcid":false,"given":"Dinesh R","family":"Katti","sequence":"additional","affiliation":[{"name":"Center for Engineered Cancer Testbeds North Dakota State University  Fargo ND USA"},{"name":"Department of Civil and Environmental Engineering North Dakota State University  Fargo ND USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jairam","family":"Iswara","sequence":"additional","affiliation":[{"name":"Department of Urology, Saint Elizabeth's Medical Center Tufts University  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renugopalakrishnan","family":"Venkatesan","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Chemical Biology Northeastern University  Boston MA USA"},{"name":"Center for Life Sciences Boston Children's Hospital, Harvard Medical School, Boston  Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramasamy","family":"Paulmurugan","sequence":"additional","affiliation":[{"name":"Department of Radiology Cellular Pathway Imaging Laboratory (CPIL), Stanford University School of Medicine  Palo Alto CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1404-4018","authenticated-orcid":false,"given":"Kalpana S","family":"Katti","sequence":"additional","affiliation":[{"name":"Center for Engineered Cancer Testbeds North Dakota State University  Fargo ND USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,12,30]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1053\/hp.2000.6698"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.405"},{"key":"e_1_2_8_4_1","volume-title":"SEER Cancer Statistics Review, 1975\u20132014","author":"Howlader N","year":"2017"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.2300"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000658-194007000-00016"},{"issue":"4","key":"e_1_2_8_7_1","first-page":"293","article-title":"Studies on prostatic cancer \u2010 I the effect of castration, of estrogen and of androgen injection on serum phosphatases in metastatic carcinoma of the prostate","volume":"1","author":"Huggins C","year":"1941","journal-title":"Cancer Res."},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.6317"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.urology.2004.05.036"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.3618"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0603090103"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.10276"},{"key":"e_1_2_8_13_1","doi-asserted-by":"crossref","unstructured":"KomoriT.Roles of Runx2 in skeletal development. 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