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Human umbilical cord mesenchymal stem cells inhibit C6 glioma growth via secretion of dickkopf-1 (DKK1)

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Abstract

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.

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Acknowledgments

This study was supported by the Program for New Century Excellent Talents in University (No. NECT-06-0611), National Science Foundation of China (81071008, 81171177), and the “Strategic Priority Research Program” of the Chinese Academy of Sciences (XDA01030300). 211 Project-phase Ш of Zhengzhou University-the basic and clinical research of stem cells, the Excellent Youth Foundation of He’nan Scientific Committee (114100510005). We thank Professor Fusheng Liu of Beijing Neurosurgical Institute, China, for the generous gift of C6 cells.

Conflict of interest

The authors state no conflicts of interest.

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Authors and Affiliations

  1. School of Life Sciences, Zhengzhou University, Zhengzhou, 450001, Henan, China

    Shanshan Ma, Shuo Liang, Liankai Chi, Xinyi Shi & Fangxia Guan

  2. Biotherapy Center, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, 471003, Henan, China

    Shuo Liang

  3. Department of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China

    Hongliang Jiao, Yi Tian & Bo Yang

  4. Henan Academy of Medical Sciences, Zhengzhou, 450003, Henan, China

    Fangxia Guan

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  1. Shanshan Ma
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  2. Shuo Liang
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  3. Hongliang Jiao
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  4. Liankai Chi
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  7. Bo Yang
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Corresponding authors

Correspondence to Bo Yang or Fangxia Guan.

Additional information

Shanshan Ma and Shuo Liang contributed equally to this work.

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Ma, S., Liang, S., Jiao, H. et al. Human umbilical cord mesenchymal stem cells inhibit C6 glioma growth via secretion of dickkopf-1 (DKK1). Mol Cell Biochem 385, 277–286 (2014). https://doi.org/10.1007/s11010-013-1836-y

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  • DOI: https://doi.org/10.1007/s11010-013-1836-y

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