通过振荡流体流动的骨细胞机械负荷调节早期PC-3前列腺癌骨转移。

IF 3.2 3区 生物学 Q3 MATERIALS SCIENCE, BIOMATERIALS
Kimberly Seaman, Chun-Yu Lin, Xin Song, Amel Sassi, William W. Du, Burton Yang, Yu Sun, Lidan You
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引用次数: 0

摘要

骨转移是晚期前列腺癌患者的致命并发症。骨细胞作为骨中主要的机械传感器,近年来在前列腺癌骨转移中的作用得到了研究。体内研究结果显示运动作为骨转移的预防性干预策略的潜在益处。相反,体外研究表明,在机械负荷下,前列腺癌与骨细胞的直接相互作用促进了前列腺癌的生长和迁移。这些发现与体内结果不一致,可能更多地反映了晚期转移性定植。本文研究了血流刺激骨细胞在早期骨转移中的作用,特别是前列腺癌内皮相互作用。与静态对照相比,血流刺激的骨细胞可使PC-3前列腺癌细胞粘附和跨内皮迁移分别减少32.3%和40%。在微流控组织模型中,机械负荷下MLO-Y4和原代小鼠骨细胞均可调节PC-3细胞外渗的距离和频率。血管细胞粘附分子1 (VCAM-1)中和抗体的应用消除了静态和血流刺激组之间癌细胞粘附、外渗频率和外渗PC-3细胞数量的差异。综上所述,本文以PC-3细胞为模型证明了骨细胞在早期骨转移中的作用,弥合了体外和体内研究结果之间的差距。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Mechanical Loading of Osteocytes via Oscillatory Fluid Flow Regulates Early-Stage PC-3 Prostate Cancer Metastasis to Bone

Mechanical Loading of Osteocytes via Oscillatory Fluid Flow Regulates Early-Stage PC-3 Prostate Cancer Metastasis to Bone

Bone metastasis is a devastating complication for advanced-stage prostate cancer patients. 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-osteocyte 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-stage metastatic colonization. Here, the role of flow-stimulated osteocytes during early-stage bone metastasis, particularly prostate cancer-endothelial interactions, is examined. Flow-stimulated osteocytes reduce PC-3 prostate cancer cell adhesion and trans-endothelial migration by 32.3% and 40% compared to static controls. Both MLO-Y4 and primary murine osteocytes under mechanical loading regulate the extravasation distance and frequency of PC-3 cells in a microfluidic tissue model. Application of vascular cellular adhesion molecule 1 (VCAM-1) neutralizing antibody abolishes the difference in cancer cell adhesion, extravasation frequency, and number of extravasated PC-3 cells between static and flow-stimulated groups. Taken together, the role of osteocytes in early-stage bone metastasis using PC-3 cells as a model is demonstrated here, bridging the gap between in vitro and in vivo findings.

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来源期刊
Advanced biology
Advanced biology Biochemistry, Genetics and Molecular Biology-Biochemistry, Genetics and Molecular Biology (all)
CiteScore
6.60
自引率
0.00%
发文量
130
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