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Side population cells in human gallbladder cancer cell line GBC-SD regulated by TGF-β-induced epithelial-mesenchymal transition

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Summary

Mounting evidence has shown that side population (SP) cells are enriched for cancer stem cells (CSCs) responsible for cancer malignancy. In this study, SP technology was used to isolate a small subpopulation of SP cells in human gallbladder cancer cell line GBC-SD, and SP cells which had superior potential for proliferation in vitro and tumorigenesis in vivo were identified. Importantly, the abundance of GBC-SD SP cells was increased by a transforming growth factor-β (TGF-β)-induced epithelial-mesenchymal transition (EMT), and this effect was accompanied with a strong up-regulation of ABCG2 mRNA expression, and a decreased sensitivity to mitoxantrone. SP cells were restored upon the removal of TGF-β and the reversion of the cells to an epithelial phenotype, and smad3-specific siRNA reduced SP abundance in response to TGF-β. In conclusion, TGF-β-induced EMT by smad-dependent signaling pathway promotes cancer development and anti-cancer drug resistant phenotype by augmenting the abundance of GBC-SD SP cells, and a better understanding of mechanisms involved in TGF-β-induced EMT may provide a novel strategy for preventing cancer progression.

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Authors and Affiliations

  1. Department of Biliary-pancreatic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

    Zhifa Zhang  (张志发), Feng Zhu  (朱 峰), Min Wang  (王 敏), Rui Tian  (田 锐), Chengjian Shi  (石程剑) & Renyi Qin  (秦仁义)

  2. Department of Chemical and Materials, College of Science, Naval University of Engineering, Wuhan, 430030, China

    Ling Xiao  (肖 玲)

Authors
  1. Zhifa Zhang  (张志发)
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  2. Feng Zhu  (朱 峰)
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  3. Ling Xiao  (肖 玲)
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  4. Min Wang  (王 敏)
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  5. Rui Tian  (田 锐)
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  6. Chengjian Shi  (石程剑)
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  7. Renyi Qin  (秦仁义)
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Corresponding author

Correspondence to Renyi Qin  (秦仁义).

Additional information

The authors contributed equally to this work.

This project was supported by a grant from the National Natural Science Foundation of China (No. 30772127).

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Zhang, Z., Zhu, F., Xiao, L. et al. Side population cells in human gallbladder cancer cell line GBC-SD regulated by TGF-β-induced epithelial-mesenchymal transition. J. Huazhong Univ. Sci. Technol. [Med. Sci.] 31, 749–755 (2011). https://doi.org/10.1007/s11596-011-0671-1

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  • DOI: https://doi.org/10.1007/s11596-011-0671-1

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