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Osteocytes, as the primary mechanosensors in bone, have been recently investigated for their role in prostate cancer bone metastasis. In vivo findings show potential benefits of exercise as a preventative intervention strategy for bone metastasis. In contrast, in vitro studies indicate direct prostate cancer\u2010osteocyte interactions under mechanical loading promote prostate cancer growth and migration. These findings are not consistent with in vivo results and may be more reflective of late\u2010stage metastatic colonization. Here, the role of flow\u2010stimulated osteocytes during early\u2010stage bone metastasis, particularly prostate cancer\u2010endothelial interactions, is examined. Flow\u2010stimulated osteocytes reduce PC\u20103 prostate cancer cell adhesion and trans\u2010endothelial migration by 32.3% and 40% compared to static controls. Both MLO\u2010Y4 and primary murine osteocytes under mechanical loading regulate the extravasation distance and frequency of PC\u20103 cells in a microfluidic tissue model. Application of vascular cellular adhesion molecule 1 (VCAM\u20101) neutralizing antibody abolishes the difference in cancer cell adhesion, extravasation frequency, and number of extravasated PC\u20103 cells between static and flow\u2010stimulated groups. Taken together, the role of osteocytes in early\u2010stage bone metastasis using PC\u20103 cells as a model is demonstrated here, bridging the gap between in vitro and in vivo findings.<\/jats:p>","DOI":"10.1002\/adbi.202400824","type":"journal-article","created":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T10:10:21Z","timestamp":1739959821000},"source":"Crossref","is-referenced-by-count":3,"title":["Mechanical Loading of Osteocytes via Oscillatory Fluid Flow Regulates Early\u2010Stage PC\u20103 Prostate Cancer Metastasis to Bone"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-9797-8530","authenticated-orcid":false,"given":"Kimberly","family":"Seaman","sequence":"first","affiliation":[{"name":"Department of Mechanical and Industrial Engineering University of Toronto  Toronto Ontario M5S 3G8 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun\u2010Yu","family":"Lin","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Engineering University of Toronto  Toronto Ontario M5S 3G9 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Mechanical and Industrial Engineering University of Toronto  Toronto Ontario M5S 3G8 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amel","family":"Sassi","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Engineering University of Toronto  Toronto Ontario M5S 3G9 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William W.","family":"Du","sequence":"additional","affiliation":[{"name":"Sunnybrook Research Institute and Department of Laboratory Medicine and Pathobiology University of Toronto  Toronto Ontario M4N 3M5 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Burton","family":"Yang","sequence":"additional","affiliation":[{"name":"Sunnybrook Research Institute and Department of Laboratory Medicine and Pathobiology University of Toronto  Toronto Ontario M4N 3M5 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Mechanical and Industrial Engineering University of Toronto  Toronto Ontario M5S 3G8 Canada"},{"name":"Institute of Biomedical Engineering University of Toronto  Toronto Ontario M5S 3G9 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8889-4173","authenticated-orcid":false,"given":"Lidan","family":"You","sequence":"additional","affiliation":[{"name":"Department of Mechanical and Industrial Engineering University of Toronto  Toronto Ontario M5S 3G8 Canada"},{"name":"Institute of Biomedical Engineering University of Toronto  Toronto Ontario M5S 3G9 Canada"},{"name":"Department of Mechanical and Materials Engineering Queen's University  Kingston Ontario K7L 3N6 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,2,19]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.22742"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trecan.2020.09.006"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2020.07.003"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers15051518"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-06-1007"},{"key":"e_1_2_9_6_1","first-page":"753","volume":"4","author":"Roodman G. 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