The Institute of Translational Medicine, Tianjin Union Medical Center of Nankai University, Tianjin, China.
Clin Transl Oncol. 2022 May;24(5):892-901. doi: 10.1007/s12094-021-02740-4. Epub 2021 Dec 2.
The aim of this study was to investigate the involvement of the SDF-1/CXCR4 axis in the process of BMMSC homing in prostate cancer (PCa) in vivo and in vitro.
After verification of BMMSCs, we fixed the concentration gradient of SDF-1 for BMMSC cultivation to analyze CXCR4 expression by qRT-PCR and flow cytometric analysis. Furthermore, we developed a non-contact co-culture system and explored the participation of the SDF-1/CXCR4 axis in PCa using qRT-PCR, flow cytometry, and ELISA. In addition, A green fluorescent protein (GFP)-transplanted methylnitrosourea (MNU)-induced PCa mouse model was established to investigate the CXCR4 expression in vivo.
The CXCR4 expression was up-regulated with the increase in SDF-1 concentrations, and elevated SDF-1 had a significant promoting effect on cell proliferation and migration in BMMSCs. Moreover, the CXCR4 expression of BMMSCs was significantly increased in the non-contact co-culture model with vascular endothelial cells (VECs), and analysis of this model also showed that the proliferation and migration of BMMSCs were promoted in the presence of VECs. The ELISA assay showed that the SDF-1 levels in the co-culture model at 48 h were significantly increased. Twenty of the GFP-transplanted mice were divided into a PCa group and a control group, and four GFP-transplanted mice were observed to have prostate tumorigenesis. It also showed that CXCR4 was obviously increased in the prostate tissue of PCa mice.
Our findings suggest that BMMSCs could home and promote the proliferation and migration of PCa through the SDF-1/CXCR4 axis in vivo and in vitro.
本研究旨在探讨 SDF-1/CXCR4 轴在体内和体外前列腺癌（PCa）骨髓间充质干细胞（BMMSC）归巢过程中的作用。
在验证 BMMSC 后，我们固定 SDF-1 浓度梯度进行 BMMSC 培养，通过 qRT-PCR 和流式细胞术分析 CXCR4 表达。此外，我们开发了一种非接触共培养系统，并通过 qRT-PCR、流式细胞术和 ELISA 探索 SDF-1/CXCR4 轴在 PCa 中的参与。此外，建立了绿色荧光蛋白（GFP）转甲基亚硝脲（MNU）诱导的 PCa 小鼠模型，以研究体内 CXCR4 表达。
随着 SDF-1 浓度的增加，CXCR4 表达上调，升高的 SDF-1 对 BMMSC 增殖和迁移有显著促进作用。此外，在与血管内皮细胞（VEC）的非接触共培养模型中，BMMSC 的 CXCR4 表达显著增加，对该模型的分析也表明，在存在 VEC 的情况下，BMMSC 的增殖和迁移得到促进。ELISA 检测显示，48 小时共培养模型中的 SDF-1 水平显著升高。20 只 GFP 移植小鼠分为 PCa 组和对照组，4 只 GFP 移植小鼠观察到前列腺肿瘤发生。还表明，PCa 小鼠前列腺组织中 CXCR4 明显增加。
我们的研究结果表明，BMMSC 可以通过体内和体外 SDF-1/CXCR4 轴归巢并促进 PCa 的增殖和迁移。
