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However, current evidence for the role of integrins in breast cancer progression is contradictory and seems to be dependent on tumor stage, differentiation status, and microenvironmental influences. While some studies suggest that loss of \u03b12\u03b21 enhances cancer metastasis, other studies suggest that this integrin is pro-tumorigenic. However, few studies have looked at \u03b12\u03b21 in the context of bone metastasis. In this study, we aimed to understand the role of \u03b12\u03b21 integrin in breast cancer metastasis to bone. To address this, we utilized in vivo models of breast cancer metastasis to bone using MDA-MB-231 cells transfected with an \u03b12 expression plasmid (MDA-OE\u03b12). MDA cells overexpressing the \u03b12 integrin subunit had increased primary tumor growth and dissemination to bone but had no change in tumor establishment and bone destruction. Further in vitro analysis revealed that tumors in the bone have decreased \u03b12\u03b21 expression and increased osteolytic signaling compared to primary tumors. Taken together, these data suggest an inverse correlation between \u03b12\u03b21 expression and bone-metastatic potential. Inhibiting \u03b12\u03b21 expression may be beneficial to limit the expansion of primary tumors but could be harmful once tumors have established in bone.<\/jats:p>","DOI":"10.3390\/ijms22136906","type":"journal-article","created":{"date-parts":[[2021,6,27]],"date-time":"2021-06-27T22:24:57Z","timestamp":1624832697000},"page":"6906","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Biphasic \u03b12\u03b21 Integrin Expression in Breast Cancer Metastasis to Bone"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1270-9650","authenticated-orcid":false,"given":"Milene N.O.","family":"Moritz","sequence":"first","affiliation":[{"name":"Program in Evolutionary Genetics and Molecular Biology, Federal University of Sao Carlos, Sao Carlos, SP 13565-905, Brazil"},{"name":"Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6498-4211","authenticated-orcid":false,"given":"Alyssa R.","family":"Merkel","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA"},{"name":"Center for Bone Biology, Vanderbilt University Medical Center, Nashville, TN 37232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ean G.","family":"Feldman","sequence":"additional","affiliation":[{"name":"Vanderbilt Graduate School Program in Biomedical Sciences, Vanderbilt University Medical Center, Nashville, TN 37232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heloisa S.","family":"Selistre-de-Araujo","sequence":"additional","affiliation":[{"name":"Program in Evolutionary Genetics and Molecular Biology, Federal University of Sao Carlos, Sao Carlos, SP 13565-905, Brazil"},{"name":"Department of Physiological Sciences, Federal University of Sao Carlos, Sao Carlos, SP 13565-905, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie A.","family":"Rhoades (Sterling)","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA"},{"name":"Center for Bone Biology, Vanderbilt University Medical Center, Nashville, TN 37232, USA"},{"name":"Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, TN 37232, USA"},{"name":"Veterans\u2019 Affairs Tennessee Valley Healthcare System, Nashville, TN 37232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,27]]},"reference":[{"key":"ref_1","unstructured":"American Cancer Society (2020). 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