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Pre-treatment of human umbilical cord-derived mesenchymal stem cells with interleukin-6 abolishes their growth-promoting effect on gastric cancer cells

  • Authors:
    • Mei Wang
    • Jie Cai
    • Feng Huang
    • Mengchu Zhu
    • Qiang Zhang
    • Tingting Yang
    • Xu Zhang
    • Hui Qian
    • Wenrong Xu
  • View Affiliations / Copyright

    Affiliations: Key Laboratory of Medical Science and Laboratory Medicine of Jiangsu Province, The Affiliated Hospital, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China
    Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].
  • Pages: 367-375
    |
    Published online on: December 2, 2014
       https://doi.org/10.3892/ijmm.2014.2019
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Abstract

The inflammatory microenvironment contributes to cancer development and progression. Mesenchymal stem cells (MSCs), as important stromal cells, may be ‘educated’ by the inflammatory microenvironment to support the development of gastric cancer. Cytokines are a key component of cancer-related inflammation. Interleukin (IL)-6, as an inflammatory cytokine, has multiple roles in cancer. However, whether MSCs can be ‘educated’ by IL-6 to support gastric cancer remains unknown. In the present study, we focused on the phenotype and function of human umbilical cord-derived MSCs hUC‑MSCs pre-treated with IL-6 in gastric cancer. We found that the protein levels of α-smooth muscle actin (α-SMA) were upregulated, and phosphorylated nuclear factor (NF)-κB protein levels were downregulated in the hUC‑MSCs pre-treated with IL-6, as shown by western blot analysis. The levels of tumor‑promoting cytokines, including chemokine (C-C motif) ligand 5 (CCL5), platelet-derived growth factor‑BB (PDGF‑BB), monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor α(TNFα), were markedly reduced in the hUC‑MSCs following treatment with IL-6, as shown by RT-qPCR. In in vitro experiments, we co-cultured MSCs with N-methyl‑N'‑nitro‑N‑nitrosoguanidine (MNNG)‑transformed GES-1 gastric epithelial cells or SGC-7901 gastric cancer cells. Transwell and colony-forming cell assays revealed that the hUC-MSCs significantly promoted gastric cellular migration and proliferation. However, following treatment with IL-6, the hUC-MSCs had no growth-promoting effect on the gastric epithelial cells and gastric cancer cells. In in vivo experiments, we co-transplanted MSCs and SGC-7901 cells into nude mice in order to establish a nude mouse model of gastric cancer. The hUC-MSCs significantly promoted the growth gastric tumors through the promotion of cell proliferation and the inhibition of cell apoptosis. On the contrary, pre-treatment with IL-6 provided the hUC‑MSCs with the ability to inhibit cell proliferation and significantly induce cell apoptosis. Taken together, our findings indicate that pre-treatment with IL-6 significantly abolishes the ability of hUC-MSCs to promote gastric epithelial cell proliferation and migration and provide new insight into the effects of the inflammatory cytokine, IL-6, on the tumor-promoting ability of MSCs and its role in gastric cancer.
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Copy and paste a formatted citation
Spandidos Publications style
Wang M, Cai J, Huang F, Zhu M, Zhang Q, Yang T, Zhang X, Qian H and Xu W: Pre-treatment of human umbilical cord-derived mesenchymal stem cells with interleukin-6 abolishes their growth-promoting effect on gastric cancer cells. Int J Mol Med 35: 367-375, 2015.
APA
Wang, M., Cai, J., Huang, F., Zhu, M., Zhang, Q., Yang, T. ... Xu, W. (2015). Pre-treatment of human umbilical cord-derived mesenchymal stem cells with interleukin-6 abolishes their growth-promoting effect on gastric cancer cells. International Journal of Molecular Medicine, 35, 367-375. https://doi.org/10.3892/ijmm.2014.2019
MLA
Wang, M., Cai, J., Huang, F., Zhu, M., Zhang, Q., Yang, T., Zhang, X., Qian, H., Xu, W."Pre-treatment of human umbilical cord-derived mesenchymal stem cells with interleukin-6 abolishes their growth-promoting effect on gastric cancer cells". International Journal of Molecular Medicine 35.2 (2015): 367-375.
Chicago
Wang, M., Cai, J., Huang, F., Zhu, M., Zhang, Q., Yang, T., Zhang, X., Qian, H., Xu, W."Pre-treatment of human umbilical cord-derived mesenchymal stem cells with interleukin-6 abolishes their growth-promoting effect on gastric cancer cells". International Journal of Molecular Medicine 35, no. 2 (2015): 367-375. https://doi.org/10.3892/ijmm.2014.2019
Copy and paste a formatted citation
x
Spandidos Publications style
Wang M, Cai J, Huang F, Zhu M, Zhang Q, Yang T, Zhang X, Qian H and Xu W: Pre-treatment of human umbilical cord-derived mesenchymal stem cells with interleukin-6 abolishes their growth-promoting effect on gastric cancer cells. Int J Mol Med 35: 367-375, 2015.
APA
Wang, M., Cai, J., Huang, F., Zhu, M., Zhang, Q., Yang, T. ... Xu, W. (2015). Pre-treatment of human umbilical cord-derived mesenchymal stem cells with interleukin-6 abolishes their growth-promoting effect on gastric cancer cells. International Journal of Molecular Medicine, 35, 367-375. https://doi.org/10.3892/ijmm.2014.2019
MLA
Wang, M., Cai, J., Huang, F., Zhu, M., Zhang, Q., Yang, T., Zhang, X., Qian, H., Xu, W."Pre-treatment of human umbilical cord-derived mesenchymal stem cells with interleukin-6 abolishes their growth-promoting effect on gastric cancer cells". International Journal of Molecular Medicine 35.2 (2015): 367-375.
Chicago
Wang, M., Cai, J., Huang, F., Zhu, M., Zhang, Q., Yang, T., Zhang, X., Qian, H., Xu, W."Pre-treatment of human umbilical cord-derived mesenchymal stem cells with interleukin-6 abolishes their growth-promoting effect on gastric cancer cells". International Journal of Molecular Medicine 35, no. 2 (2015): 367-375. https://doi.org/10.3892/ijmm.2014.2019
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