{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T17:51:30Z","timestamp":1792000290748,"version":"4.4.0"},"reference-count":40,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T00:00:00Z","timestamp":1762905600000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Cellular Biochemistry"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Bone morphogenetic protein\u20109 (BMP9) has been implicated as a regulator of metastasis and tumor angiogenesis, with contrasting studies demonstrating both pro\u2010 and antiangiogenic roles for BMP9 across different cancer cell lines and animal models. However, these works have yet to define the contribution of the type\u2010II BMP receptor (BMPR\u2010II) to these processes, or assess whether the effects of BMP9 are mediated via actions on the endothelium, the tumor, or its microenvironment. Here, we demonstrate that the heterozygous (\n                    <jats:italic>Bmpr2<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>EC+\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    ) or homozygous (\n                    <jats:italic>Bmpr2<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>EC\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    ) deletion of BMPR\u2010II in the pulmonary endothelium is associated with increased overall burden and vascularization of metastases in the lungs of mice subjected to the EO771 orthotopic engraftment model of metastatic breast cancer. These increases, relative to\n                    <jats:italic>Bmpr2<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>EC+\/+<\/jats:italic>\n                    <\/jats:sup>\n                    littermates, were observed despite equivalent primary mammary tumor growth across mice of all genotypes.\n                    <jats:italic>In vitro<\/jats:italic>\n                    , secreted factors or extracellular matrix components from BMPR\u2010II\u2010silenced human pulmonary arterial endothelial cells (HPAECs) did not alter EO771 proliferation relative to controls. However, endothelial BMPR\u2010II depletion did eliminate the capacity of BMP9 to suppress both HPAEC migration to VEGF\n                    <jats:sub>165<\/jats:sub>\n                    and EO771 transmigration across an HPAEC monolayer. In a tail vein injection model, the short\u2010term establishment of EO771 cell metastatic lesions was equivalent in the lungs of female\n                    <jats:italic>Bmpr2<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>EC+\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    and\n                    <jats:italic>Bmpr2<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>EC\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    mice, relative to\n                    <jats:italic>Bmpr2<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>EC+\/+<\/jats:italic>\n                    <\/jats:sup>\n                    controls, suggesting that the enhanced lung tumor burden observed in orthotopically implanted mice with endothelial\n                    <jats:italic>Bmpr2<\/jats:italic>\n                    deletion is likely a consequence of enhanced tumor vascularization, rather than altered lung retention and engraftment. Our findings identify an important role for endothelial BMPR\u2010II signaling in regulating the vascularization of metastatic lesions in the lungs.\n                  <\/jats:p>","DOI":"10.1002\/jcb.70071","type":"journal-article","created":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T11:27:22Z","timestamp":1762946842000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<i>Bmpr2<\/i>\n                    Loss in the Vascular Endothelium Enhances Neoangiogenesis and Growth of Lung Metastatic Lesions in a Mouse Model of Breast Cancer"],"prefix":"10.1002","volume":"126","author":[{"given":"Jordan A.","family":"Harry","sequence":"first","affiliation":[{"name":"Department of Medicine Queen's University Kingston Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia I.","family":"Skebo","sequence":"additional","affiliation":[{"name":"Department of Medicine Queen's University Kingston Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Devon V.","family":"Cole","sequence":"additional","affiliation":[{"name":"Department of Medicine Queen's University Kingston Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Dinh","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Molecular Sciences Queen's University Kingston Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Martin","family":"VandenBroek","sequence":"additional","affiliation":[{"name":"Department of Medicine Queen's University Kingston Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abby K.","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Medicine Queen's University Kingston Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natasha","family":"Camacho","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Molecular Sciences Queen's University Kingston Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hollie N.","family":"Piepjohn","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Molecular Sciences Queen's University Kingston Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Hoskin","sequence":"additional","affiliation":[{"name":"Department of Pathology and Molecular Medicine Queen's University Kingston Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly J.","family":"Laverty","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Molecular Sciences Queen's University Kingston Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Pathology and Molecular Medicine Queen's University Kingston Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas","family":"Quilty","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Molecular Sciences Queen's University Kingston Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter A.","family":"Greer","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Molecular Sciences Queen's University Kingston Ontario Canada"},{"name":"Department of Pathology and Molecular Medicine Queen's University Kingston Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark L.","family":"Ormiston","sequence":"additional","affiliation":[{"name":"Department of Medicine Queen's University Kingston Ontario Canada"},{"name":"Department of Biomedical and Molecular Sciences Queen's University Kingston Ontario Canada"},{"name":"Department of Surgery Queen's University Kingston Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,11,12]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1511814112"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)65006-7"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)63273-7"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10549-005-9117-4"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21551"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-07-5644"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.22041"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1530\/ERC-17-0309"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2010.30.0855"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-13-0081"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.3747\/co.22.2210"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.14.9930"},{"key":"e_1_2_10_14_1","first-page":"3369","article-title":"The Antiangiogenic Property of Docetaxel Is Synergistic With a Recombinant Humanized Monoclonal Antibody Against Vascular Endothelial Growth Factor or 2\u2010Methoxyestradiol But Antagonized by Endothelial Growth Factors","volume":"61","author":"Sweeney C. 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