Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200011, P.R. China.
Mol Med Rep. 2013 Nov;8(5):1486-92. doi: 10.3892/mmr.2013.1698. Epub 2013 Sep 23.
Bone is a major site of metastasis for several types of malignant tumor. Specific interactions between tumor cells and the bone microenvironment contribute to the tendency of tumors to metastasize to bone. Furthermore, Wnt5a participates in the progression of several types of malignant tumor. This study investigates the role of Wnt5a in the migration of the prostate cancer (PCa) cell line PC3 toward bone marrow stromal cell (BMSC)‑conditioned medium (CM). The expression of 22 genes associated with bone metastasis was measured in three PCa cell lines (LNCaP, PC3 and DU145). Subsequently, the proliferation and migration capacities of PC3 cells treated either with small interfering RNA (siRNA) against Wnt5a or with recombinant mouse (rm) Wnt5a were analyzed with alamarBlue and transwell assays. BMSC‑CM was collected to evaluate its effect on PC3 cell migration. Also, the expression of Wnt5a in BMSCs was knocked down prior to collection of the CM to evaluate its effects on the migration of PC3 cells. Significantly higher levels of Wnt5a mRNA expression were identified in the PC3 cells, compared with those in LNCaP and DU145 cells. Silencing Wnt5a expression with siRNA reduced the migration capacity of PC3 cells by 50%. The addition of rmWnt5a improved the migration capacity of PC3 cells in a concentration‑dependent manner. PC3 cells preferred to migrate toward BMSC‑CM than toward the control. CM from Wnt5a siRNA‑treated BMSCs significantly reduced PC3 cell migration. Wnt5a promotes PC3 cell migration toward BMSC‑CM, indicating that Wnt5a is a potential therapeutic target for the treatment of advanced PCa.
骨骼是多种恶性肿瘤转移的主要部位。肿瘤细胞与骨微环境之间的特定相互作用促进了肿瘤向骨骼转移的趋势。此外，Wnt5a 参与了多种恶性肿瘤的进展。本研究探讨了 Wnt5a 在前列腺癌细胞系 PC3 向骨髓基质细胞（BMSC）条件培养基（CM）迁移中的作用。在三种前列腺癌细胞系（LNCaP、PC3 和 DU145）中测量了与骨转移相关的 22 个基因的表达。随后，通过 alamarBlue 和 Transwell 测定分析了用 Wnt5a 小干扰 RNA（siRNA）或重组鼠（rm）Wnt5a 处理的 PC3 细胞的增殖和迁移能力。收集 BMSC-CM 以评估其对 PC3 细胞迁移的影响。此外，在收集 CM 之前敲低 BMSCs 中的 Wnt5a 表达，以评估其对 PC3 细胞迁移的影响。与 LNCaP 和 DU145 细胞相比，PC3 细胞中 Wnt5a mRNA 表达水平明显更高。用 siRNA 沉默 Wnt5a 表达可使 PC3 细胞的迁移能力降低 50%。rmWnt5a 的添加以浓度依赖的方式改善了 PC3 细胞的迁移能力。PC3 细胞更倾向于向 BMSC-CM 迁移，而不是向对照迁移。来自 Wnt5a siRNA 处理的 BMSCs 的 CM 显著降低了 PC3 细胞的迁移。Wnt5a 促进 PC3 细胞向 BMSC-CM 的迁移，表明 Wnt5a 是治疗晚期前列腺癌的潜在治疗靶点。
