Tumor Biology

, Volume 35, Issue 10, pp 9667–9676 | Cite as

BMP-7 blocks the effects of TGF-β-induced EMT in cholangiocarcinoma

  • Kassaporn Duangkumpha
  • Anchalee Techasen
  • Watcharin Loilome
  • Nisana Namwat
  • Raynoo Thanan
  • Narong Khuntikeo
  • Puangrat Yongvanit
Research Article

Abstract

Epithelial–mesenchymal transition (EMT) is characterized by the loss of epithelial markers and the gain of mesenchymal markers. EMT is believed to be a major mechanism supporting cancer cell metastasis. The activation of EMT can be induced by various types of inflammatory cytokines including transforming growth factor β (TGF-β) whereas bone morphogenetic protein-7 (BMP-7) can inhibit this process. In this study, the up-regulation of Twist transcription factor and N-cadherin, mesenchymal marker in CCA tissues, has been demonstrated and it has been found that the high expression of Twist was significantly associated with poor prognosis of CCA patients (P = 0.010). Moreover, CCA samples showing Twist nuclear expression were significantly correlated with the up-regulation of N-cadherin (P = 0.024). These results also showed that the inflammatory mediator TGF-β induces CCA cell migration, one of the metastatic processes possibly via stimulation of Twist, N-cadherin and vimentin expression. Additionally, it has been shown that BMP-7 inhibits TGF-β-induced CCA cell migration, through inhibition of TGF-β-mediated Twist and N-cadherin expressions. These data reinforce the rationale to use BMP-7 as an EMT inhibitor to suppress the progression of CCA and might be a therapeutic approach to improve efficiency for CCA treatment.

Keywords

Twist N-cadherin Metastasis Epithelial–mesenchymal transition BMP-7 Cholangiocarcinoma 

Notes

Acknowledgments

This work was supported by the Higher Education Research Promotion and National Research University Project of Thailand, Office of the Higher Education Commission, through the Health Cluster (SHeP-GMS), Khon Kaen University, Khon Kaen University Research Fund to PY and KD (Grant No. M54206) and the grant of Faculty of Medicine to KD (Grant No. I 56316). We express our sincere thanks to Professor James A Will for checking scientific and English improvements.

Conflicts of interest

None

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Kassaporn Duangkumpha
    • 1
    • 4
  • Anchalee Techasen
    • 2
    • 4
  • Watcharin Loilome
    • 1
    • 4
  • Nisana Namwat
    • 1
    • 4
  • Raynoo Thanan
    • 1
    • 4
  • Narong Khuntikeo
    • 3
    • 4
  • Puangrat Yongvanit
    • 1
    • 4
  1. 1.Department of Biochemistry, Faculty of MedicineKhon Kaen UniversityKhon KaenThailand
  2. 2.Center for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical SciencesKhon Kaen UniversityKhon KaenThailand
  3. 3.Department of Surgery, Faculty of MedicineKhon Kaen UniversityKhon KaenThailand
  4. 4.Liver Fluke and Cholangiocarcinoma Research CenterKhon Kaen UniversityKhon KaenThailand

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