Human umbilical cord mesenchymal stem cells inhibit C6 glioma growth via secretion of dickkopf-1 (DKK1)
Human umbilical cord mesenchymal stem cells inhibit C6 glioma growth via secretion of dickkopf-1 (DKK1)
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人脐带间充质干细胞通过分泌 dickkopf-1 (DKK1) 抑制 C6 神经胶质瘤生长
DOI：
10.1007/s11010-013-1836-y
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发表时间：
2014-01-01
影响因子：
4.3
通讯作者：
Guan, Fangxia
中科院分区：
文献类型：
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作者：
Ma, Shanshan;Liang, Shuo;Guan, Fangxia
间充质干细胞（Mesenchymal stem cells，MSCs）是胶质瘤治疗的潜在靶点。本研究旨在探讨人脐带间充质干细胞（human umbilical cord-derived MSCs，hUC-MSCs）抑制C6胶质瘤细胞生长的分子机制。我们证明hUC-MSCs抑制C6细胞的生长，并将细胞周期调节至G 0/G1期。hUC-MSCs条件培养液可下调C6细胞β-catenin和c-Myc的表达，且DKK 1的分泌水平与hUCMSCs-CM浓度呈正相关。随着DKK 1浓度的增加，hUC-MSCs对C6细胞增殖的抑制作用增强。当DKK 1被抗DKK 1抗体中和时，hUC-MSCs对C6细胞的抑制作用减弱。此外，我们发现，从hUC-MSCs转染siRNA靶向DKK 1 mRNA或pEGFPN 1-DKK 1质粒的条件培养基失去或增强的Wnt信号在C6细胞中的调节能力。因此，hUC-MSCs通过分泌Wnt通路抑制剂DKK 1抑制C6胶质瘤细胞生长，可能成为治疗恶性胶质瘤的新策略。
Mesenchymal stem cells (MSCs) represent a potential therapeutic target for glioma. We determined the molecular mechanism of inhibitory effect of human umbilical cord-derived MSCs (hUC-MSCs) on the growth of C6 glioma cells. We demonstrated that hUC-MSCs inhibited C6 cell growth and modulated the cell cycle to G0/G1 phase. The expression of β-catenin and c-Myc was downregulated in C6 cells by conditioned media from hUC-MSCs, and the levels of secreted DKK1 were positively correlated with concentrations of hUCMSCs-CM. The inhibitory effect of hUC-MSCs on C6 cell proliferation was enhanced as the concentration of DKK1 in hUCMSCs-CM increased. When DKK1 was neutralized by anti-DKK1 antibody, the inhibitory effect of hUC-MSCs on C6 cells was attenuated. Furthermore, we found that conditioned media from hUC-MSCs transfection with siRNA targeting DKK1 mRNA or pEGFPN1-DKK1 plasmid lost or enhanced the abilities to regulate the Wnt signaling in C6 cells. Therefore, hUC-MSCs inhibited C6 glioma cell growth via secreting DKK1, an inhibitor of Wnt pathway, may represent a novel therapeutic strategy for malignant glioma.