{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T00:18:06Z","timestamp":1768522686982,"version":"3.49.0"},"reference-count":63,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2020,9,21]],"date-time":"2020-09-21T00:00:00Z","timestamp":1600646400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"publisher","award":["1I01BX001957"],"award-info":[{"award-number":["1I01BX001957"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 CA163499"],"award-info":[{"award-number":["R01 CA163499"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Patients with advanced skeletal metastases arising from primary cancers including breast, lung, and prostate suffer from extreme pain, bone loss, and frequent fractures. While the importance of interactions between bone and tumors is well-established, our understanding of complex cell\u2013cell and cell\u2013microenvironment interactions remains limited in part due to a lack of appropriate 3D bone models. To improve our understanding of the influence of bone morphometric properties on the regulation of tumor-induced bone disease (TIBD), we utilized bone-like 3D scaffolds in vitro and in vivo. Scaffolds were seeded with tumor cells, and changes in cell motility, proliferation, and gene expression were measured. Genes associated with TIBD significantly increased with increasing scaffold rigidity. Drug response differed when tumors were cultured in 3D compared to 2D. Inhibitors for Integrin \u03b23 and TGF-\u03b2 Receptor II significantly reduced bone-metastatic gene expression in 2D but not 3D, while treatment with the Gli antagonist GANT58 significantly reduced gene expression in both 2D and 3D. When tumor-seeded 3D scaffolds were implanted into mice, infiltration of myeloid progenitors changed in response to pore size and rigidity. This study demonstrates a versatile 3D model of bone used to study the influence of mechanical and morphometric properties of bone on TIBD.<\/jats:p>","DOI":"10.3390\/ijms21186913","type":"journal-article","created":{"date-parts":[[2020,9,21]],"date-time":"2020-09-21T08:18:01Z","timestamp":1600676281000},"page":"6913","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["3D Bone Morphology Alters Gene Expression, Motility, and Drug Responses in Bone Metastatic Tumor Cells"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8610-4825","authenticated-orcid":false,"given":"Ushashi C.","family":"Dadwal","sequence":"first","affiliation":[{"name":"Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, TN 37212, USA"},{"name":"Department of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN 37235, USA"},{"name":"Center for Bone Biology, Vanderbilt University Medical Center, Nashville, TN 37232, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6498-4211","authenticated-orcid":false,"given":"Alyssa R.","family":"Merkel","sequence":"additional","affiliation":[{"name":"Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, TN 37212, USA"},{"name":"Center for Bone Biology, Vanderbilt University Medical Center, Nashville, TN 37232, USA"},{"name":"Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan M.","family":"Page","sequence":"additional","affiliation":[{"name":"Department of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN 37235, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristin A.","family":"Kwakwa","sequence":"additional","affiliation":[{"name":"Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, TN 37212, USA"},{"name":"Center for Bone Biology, Vanderbilt University Medical Center, Nashville, TN 37232, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Kessler","sequence":"additional","affiliation":[{"name":"School for Science and Math, Vanderbilt University, Nashville, TN 37235, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julie A.","family":"Rhoades","sequence":"additional","affiliation":[{"name":"Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, TN 37212, USA"},{"name":"Center for Bone Biology, Vanderbilt University Medical Center, Nashville, TN 37232, USA"},{"name":"Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA"},{"name":"Department of Biomedical Engineering, Vanderbilt University, Nashville, TN 37235, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.pharmthera.2015.02.002","article-title":"HIF targets in bone remodeling and metastatic disease","volume":"150","author":"Johnson","year":"2015","journal-title":"Pharmacol. 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