Osteocytes under Mechanical Loading Regulate PC-3 Cancer Cell-Mineral Interactions during Early-Stage Metastasis to...

Bone metastasis causes severe complications for patients suffering from advanced-stage prostate cancer. Exercise is recommended to help maintain musculoskeletal health during treatment. As primary mechanosensors and regulators of bone homeostasis, osteocytes recently investigate for their roles in prostate cancer bone metastasis. Recently, in vivo studies show that exercise mitigates prostate tumor progression and preserves bone structure. In contrast, in vitro studies indicate direct prostate cancer-osteocyte interactions under mechanical loading conditions promote prostate cancer growth and migration but exclude other host cells present in the metastatic bone microenvironment. Thus, these in vitro findings are not consistent with recent in vivo results. In this study, the role of mechanically stimulated osteocytes during the initial stages of metastatis in osteoblast-rich areas is examined. When treated with conditioned media from flow-stimulated osteocytes, osteoblasts reduce PC-3 wound healing migration and invasion compared to static controls. Of interest, osteoblasts treated with flow-stimulated MLO-Y4 and primary osteocyte conditioned media suppress PC-3 cancer cell growth, alter cancer cell morphology, and preserve mineralized matrix in a microfluidic co-culture assay. Overall, the inhibitory role of mechanical loading of osteocytes on the early-stage metastasis of the endosteal surface during prostate cancer bone metastasis is demonstrated.