C6胶质瘤条件培养基诱导间充质干细胞恶性转化：S100B/RAGE途径的可能作用
C6 glioma-conditioned medium induces malignant transformation of mesenchymal stem cells: Possible role of S100B/RAGE pathway.
作者信息
Tan Bin, Shen Lianju, Yang Ke, Huang Daochao, Li Xin, Li Yasha, Zhao Li, Chen Jie, Yi Qing, Xu Hao, Tian Jie, Zhu Jing
机构信息
Pediatric Research Institute, Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China; China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing, 400014, China.
Pediatric Research Institute, Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China; China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing, 400014, China; Chongqing Key Laboratory of Children Urogenital Development and Tissue Engineering, Chongqing, 400014, China.
出版信息
Biochem Biophys Res Commun. 2018 Jan 1;495(1):78-85. doi: 10.1016/j.bbrc.2017.10.071. Epub 2017 Oct 16.
Mesenchymal stem cells (MSCs) have been widely studied as an attractive therapeutic agent for the treatment of tumors. However, the adverse effects of the tumor paracrine factors who affect MSCs are still unclear. In this study, we report for the first time that C6 glioma-conditioned medium (GCM) induces malignant transformation of MSCs. In contrast to MSCs, the transformed mesenchymal stem cells (TMCs) exhibited tumor cell characterizations in vitro and highly tumorigenic in vivo. Furthermore, GCM and recombinant S100B increased receptor for advanced glycation end products (RAGE) and its downstream Akt1, STAT3 genes expression as well as phosphorylation and transcriptional activation. Finally, blockage of S100B-RAGE interaction by RAGE inhibitor FPS-ZM1 attenuated GCM and S100B-induced Akt1, STAT3 activation, abolished its cell proliferation, migration and invasion actions. Together, these results suggest that the RAGE pathway may play a possible role in malignant transformation procedure of MSCs, and that this process may be mediated through S100B.
间充质干细胞（MSCs）作为一种极具吸引力的肿瘤治疗药物已得到广泛研究。然而，影响MSCs的肿瘤旁分泌因子的不良反应仍不清楚。在本研究中，我们首次报道C6胶质瘤条件培养基（GCM）可诱导MSCs发生恶性转化。与MSCs相比，转化后的间充质干细胞（TMCs）在体外表现出肿瘤细胞特征，在体内具有高度致瘤性。此外，GCM和重组S100B增加了晚期糖基化终产物受体（RAGE）及其下游Akt1、STAT3基因的表达以及磷酸化和转录激活。最后，RAGE抑制剂FPS-ZM1阻断S100B-RAGE相互作用可减弱GCM和S100B诱导的Akt1、STAT3激活，消除其细胞增殖、迁移和侵袭作用。总之，这些结果表明RAGE途径可能在MSCs的恶性转化过程中发挥作用，并且这一过程可能通过S100B介导。
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