Yin Qiang, Zhou Yang-Yang, Wang Peng, Ma L I, Li Peng, Wang Xiao-Guang, She Chun-Hua, Li Wen-Liang
Department of Neurosurgery and Neuro-Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, P.R. China.
Division of Pulmonary Medicine, Tianjin Institute of Respiratory Diseases, Tianjin Haihe Hospital, Tianjin 300222, P.R. China.
Oncol Lett. 2016 Apr;11(4):2353-2358. doi: 10.3892/ol.2016.4270. Epub 2016 Feb 24.
Previous and studies have shown that human mesenchymal stem cells (MSCs) exhibit tropism for gliomas. However, the mechanism underlying this directed migration remains unclear. The aim of the present study was to investigate the possible mechanism underlying platelet-derived growth factor-BB (PDGF-BB)-induced chemotactic migration of bone marrow-derived MSCs (BMSCs) toward glioma. Rat glioma C6 cell-conditioned medium was utilized to evaluate the chemotactic response of BMSCs toward glioma using an migration assay. Recombinant rat PDGF-BB was added to C6 cell-conditioned medium to assess its effect on the tropism of BMSCs. The effect of PDGF-BB on the expression levels of cluster of differentiation (CD)44 in BMSCs was evaluated by reverse transcription-polymerase chain reaction (RT-PCR) and immunofluorescence assays. The results revealed that chemotactic migration was induced in BMSCs by rat glioma C6 cell-conditioned medium, which was enhanced by PDGF-BB treatment in a dose-dependent manner. Furthermore, RT-PCR and immunofluorescence assays showed that CD44 expression was upregulated in BMSCs following treatment with 40 ng/ml PDGF-BB for 12 h. Additionally, 3-h pretreatment with the anti-CD44 neutralizing antibody OX-50 was observed to attenuate the tropism of BMSCs toward glioma in the presence or absence of PDGF-BB. The results of the present study indicate that CD44 mediates the tropism of BMSCs toward glioma, and PDGF-BB promotes the migration of BMSCs toward glioma via the upregulation of CD44 expression in BMSCs. These findings suggest CD44 inhibition may be a potential therapeutic target for the treatment of glioma.
以往的研究表明,人间充质干细胞(MSCs)对胶质瘤具有趋向性。然而,这种定向迁移的潜在机制仍不清楚。本研究的目的是探讨血小板衍生生长因子-BB(PDGF-BB)诱导骨髓间充质干细胞(BMSCs)向胶质瘤趋化迁移的可能机制。利用大鼠胶质瘤C6细胞条件培养基,通过迁移试验评估BMSCs对胶质瘤的趋化反应。将重组大鼠PDGF-BB添加到C6细胞条件培养基中,以评估其对BMSCs趋向性的影响。通过逆转录-聚合酶链反应(RT-PCR)和免疫荧光试验评估PDGF-BB对BMSCs中分化簇(CD)44表达水平的影响。结果显示,大鼠胶质瘤C6细胞条件培养基可诱导BMSCs发生趋化迁移,PDGF-BB处理可使其以剂量依赖的方式增强。此外,RT-PCR和免疫荧光试验表明,用40 ng/ml PDGF-BB处理12小时后,BMSCs中CD44表达上调。此外,观察到在存在或不存在PDGF-BB的情况下,用抗CD44中和抗体OX-50预处理3小时可减弱BMSCs对胶质瘤的趋向性。本研究结果表明,CD44介导BMSCs对胶质瘤的趋向性,PDGF-BB通过上调BMSCs中CD44的表达促进BMSCs向胶质瘤迁移。这些发现表明,抑制CD44可能是治疗胶质瘤的一个潜在治疗靶点。