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Enhanced expression of trophinin promotes invasive and metastatic potential of human gallbladder cancer cells

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Abstract

Purpose

To study effects of trophinin on the metastatic potential of human gallbladder cancer cells and its potential mechanism.

Materials and methods

Expression of trophinin in the highly metastatic GBC-SDHi cells was investigated by real time RT-PCR and western blot. Recombinant expression plasmid vector of the human trophinin gene was constructed and transfected into GBC-SD cells. Effects of trophinin on the invasion of GBC-SD cells were investigated by adhesion assay and invasion assay in vitro. The siRNA was used to down-regulate the expression of trophinin. Some genes related to the invasion and metastasis of cancer were determined by real time RT-PCR and western blot. The pulmonary metastasis regulated by trophinin was determined in the nude mice.

Results

Overexpression of trophinin in GBC-SDHi cells was confirmed compared with its parental counterparts. Up-regulation of trophinin enhanced the in vitro invasion in the GBC-SD/TRO cells. The enhancement was associated with increasing integrin α3, MMP-7, MMP-9, and Ets-1 expression. The results were further demonstrated by RNA interference experiment in vitro. In in vivo study, we also demonstrated that trophinin-transfected gallbladder cancer cells had more pulmonary metastases than the vector-transfected one or its parental counterparts.

Conclusion

Overexpression of trophinin leads to a more invasive phenotype and metastatic potential in human gallbladder cancer, at least in part, through regulating integrin α3, MMP-7, MMP-9, and Ets-1 expression.

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Acknowledgments

This research was supported in part by grants from China Postdoctoral Science Foundation (20060390141).

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Authors and Affiliations

  1. Cancer Hospital and Institute, Tianjin University, 300060, Tianjin, People’s Republic of China

    Xin-Zhong Chang, Xue-Hui Zhang, Jian Yin & Xu-Chen Cao

  2. Weifang University, 261061, Weifang, People’s Republic of China

    Jie Yu

  3. Shantou University, 243 Daxue Road, 515063, Shantou, People’s Republic of China

    Tao Wang

Authors
  1. Xin-Zhong Chang
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  2. Jie Yu
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  3. Xue-Hui Zhang
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  4. Jian Yin
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  5. Tao Wang
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  6. Xu-Chen Cao
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Corresponding authors

Correspondence to Tao Wang or Xu-Chen Cao.

Additional information

X.-Z. Chang, J. Yu and X.-H. Zhang have contributed equally to this work.

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Chang, XZ., Yu, J., Zhang, XH. et al. Enhanced expression of trophinin promotes invasive and metastatic potential of human gallbladder cancer cells. J Cancer Res Clin Oncol 135, 581–590 (2009). https://doi.org/10.1007/s00432-008-0492-1

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  • DOI: https://doi.org/10.1007/s00432-008-0492-1

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