Department of Urology, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, PR China.
Mol Med Rep. 2012 Nov;6(5):955-60. doi: 10.3892/mmr.2012.1019. Epub 2012 Aug 7.
Mesenchymal stem cells (MSCs) are generally used in tissue engineering, regenerative medicine and therapy for immune disorder disease. MSCs are also employed as drug carriers for tumor therapy due to their ability to migrate to tumor tissue. However, due to the immunosuppressive function of MSCs, the application of MSCs in prostate cancer therapy remains limited. In this study, we investigated the underlying mechanism by which MSCs enable prostate cancer cells to escape from immune surveillance in the inflammatory microenvironment. Firstly, we demonstrated that compared with the control groups, MSCs pretreated with IL-1α effectively promoted the growth of the mouse prostate cancer cell line RM-1 in vivo. Furthermore, when RM-1 prostate cancer cells were co-injected with MSCs pretreated with IL-1α, tumor incidence significantly increased in allogeneic recipients. In addition, we investigated the mechanism through which MSCs promote the ability of RM-1 cells to escape from immune injury. The results revealed that IL-1α led to the upregulation of TGF-β in MSCs. The inflammatory cytokine-induced promotive effect of MSCs on RM-1 cells in vivo was inhibited by TGF-β siRNA. The results of our study suggest that inflammatory cytokines induce the immunosuppressive function of MSCs which enables prostate cancer cells to escape from immune injury.
间充质干细胞(MSCs)通常用于组织工程、再生医学和免疫紊乱疾病的治疗。由于其能够迁移到肿瘤组织,MSCs 也被用作肿瘤治疗的药物载体。然而,由于 MSCs 的免疫抑制功能,MSCs 在前列腺癌治疗中的应用仍然受到限制。在这项研究中,我们研究了 MSCs 使前列腺癌细胞在炎症微环境中逃避免疫监视的潜在机制。首先,我们证明与对照组相比,经 IL-1α 预处理的 MSCs 可有效促进小鼠前列腺癌细胞系 RM-1 在体内的生长。此外,当 RM-1 前列腺癌细胞与经 IL-1α 预处理的 MSCs 共注射时,同种异体受体中的肿瘤发生率显著增加。此外,我们研究了 MSCs 促进 RM-1 细胞逃避免疫损伤能力的机制。结果表明,IL-1α 导致 MSCs 中 TGF-β 的上调。TGF-β siRNA 抑制了炎症细胞因子在体内诱导的 MSCs 对 RM-1 细胞的促进作用。我们的研究结果表明,炎症细胞因子诱导 MSCs 的免疫抑制功能,使前列腺癌细胞逃避免疫损伤。