前列腺癌骨转移是导致美国男性癌症相关死亡的主要原因，会对骨骼组织造成严重伤害。由于药物治疗选择有限，导致生存率低，处理晚期的前列腺癌通常具有挑战性。目前对于细胞外液流生物力学刺激对前列腺癌细胞生长和迁移影响机制的认识非常匮乏。为此，我们设计了一个新颖的生物反应器系统，以展示细胞外液流对前列腺癌细胞在转移至骨骼过程中的迁移影响。首先，我们证明高流速会通过TGF-β1信号途径诱导PC3细胞凋亡，因此，生理流速条件最有利于细胞生长。接下来，为了解细胞外液流在前列腺癌细胞迁移中的作用，我们在静态和动态条件下评估了细胞在有无骨的情况下的迁移速率。我们报告称，在静态和动态条件下，CXCR4水平没有显著变化，表明CXCR4激活不受流动条件影响，而是受骨骼的影响。骨骼上调节的CXCR4水平导致MMP-9水平增加，从而在存在骨时导致高迁移速率。此外，流动条件下αvβ3整合素水平上调，对PC3细胞的迁移速率总体有所增加。总之，本研究展示了细胞外液流在前列腺癌入侵中的潜在作用。了解细胞外液流在促进前列腺癌细胞进展中的关键作用将有助于改善晚期前列腺癌的现有疗法，并为患者提供改进的治疗选项。采用署名 CC BY 许可证。

Prostate cancer bone metastasis is the leading cause of cancer-related mortality in men in the United States, causing severe damage to skeletal tissue. The treatment of advanced-stage prostate cancer is always challenging due to limited drug treatment options, resulting in low survival rates. There is a scarcity of knowledge regarding the mechanisms associated with the effects of biomechanical cues by interstitial fluid flow on prostate cancer cell growth and migration. We have designed a novel bioreactor system to demonstrate the impact of interstitial fluid flow on the migration of prostate cancer cells to the bone during extravasation. First, we demonstrated that a high flow rate induces apoptosis in PC3 cells via TGF-β1 mediated signaling; thus, physiological flow rate conditions are optimum for cell growth. Next, to understand the role of interstitial fluid flow in prostate cancer migration, we evaluated the migration rate of cells under static and dynamic conditions in the presence or absence of bone. We report that CXCR4 levels were not significantly changed under static and dynamic conditions, indicating that CXCR4 activation in PC3 cells is not influenced by flow conditions but by the bone, where CXCR4 levels were upregulated. The bone-upregulated CXCR4 levels led to increased MMP-9 levels resulting in a high migration rate in the presence of bone. In addition, upregulated levels of αvβ3 integrins under fluid flow conditions, contributed to an overall increase in the migration rate of PC3 cells. Overall, this study demonstrates the potential role of interstitial fluid flow in prostate cancer invasion. Understanding the critical role of interstitial fluid flow in promoting prostate cancer cell progression will aid in enhancing current therapies for advanced-stage prostate cancer and provide improved treatment options for patients.Creative Commons Attribution license.