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Tumor Biology

, Volume 35, Issue 10, pp 10031–10041 | Cite as

Increased EphB2 expression predicts cholangiocarcinoma metastasis

  • Walaiporn Khansaard
  • Anchalee Techasen
  • Nisana Namwat
  • Puangrat Yongvanit
  • Narong Khuntikeo
  • Anucha Puapairoj
  • Watcharin Loilome
Research Article

Abstract

The activation of Ephrin (Eph) receptors, the largest tyrosine kinase families of cell surface receptor, has recently been addressed in human cholangiocarcinoma (CCA). Therefore, the present study aimed to investigate the role of Eph receptors and its ligands in CCA. Of all 50 cases of human CCA tested, immunohistochemical staining demonstrated that EphB2, EphB4, ephrinB1, and ephrinB2 were 100 % positive in CCA tissues with overexpressions of the above proteins as 56, 56, 70, and 48 % of cases, respectively. High expression of EphB2 was significantly correlated with the metastatic status of patients (P = 0.027). We also found that the high co-expression level of EphB2/ephrinB1 or EphB2/ephrinB2 were significantly correlated with the metastatic status of the patients (P = 0.034 and P = 0.024). Furthermore, we showed that the high co-expression level of EphB4/MVD and ephrinB1/MVD were significantly correlated with the metastasis status of CCA patients (P = 0.012 and P = 0.029). We further demonstrated that the EphB2 suppression using siRNA significantly reduced CCA cell migration by decreasing the phosphorylation of focal adhesion kinase (FAK) and paxillin. In conclusion, the upregulation of EphB2 receptors and its specific ligands (ephrinB1 and ephrinB2) leads to CCA metastasis. Suppression of EphB2 expression as well as inhibition of its downstream signaling proteins might serve as possible therapeutic strategies in human CCA.

Keywords

EphB2 Tumor progression Metastasis Cholangiocarcinoma 

Notes

Acknowledgements

This study is funded by the grant from the Thailand Research Fund (Grant No. MRG5400834) and the Research Assistantship Grant of the Faculty of Medicine, Khon Kaen University (Grant No. AS55203) to WL along with the grants from the Higher Education Research Promotion and National Research University Project of Thailand, Office of the Higher Education Commission, through the Center of Excellence in Specific Health Problems in Greater Mekong Sub-region cluster (SHeP-GMS), Khon Kaen University allocated to WK and WL. We thank Prof. Ross H. Andrews for English language assistance.

Conflicts of interest

None

Supplementary material

13277_2014_2295_MOESM1_ESM.docx (38 kb)
Supplementary Table 1 (DOCX 37 kb)
13277_2014_2295_MOESM2_ESM.docx (38 kb)
Supplementary Table 2 (DOCX 38 kb)
13277_2014_2295_MOESM3_ESM.docx (36 kb)
Supplementary Table 3 (DOCX 35 kb)

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Walaiporn Khansaard
    • 1
  • Anchalee Techasen
    • 2
  • Nisana Namwat
    • 1
  • Puangrat Yongvanit
    • 1
  • Narong Khuntikeo
    • 3
  • Anucha Puapairoj
    • 4
  • Watcharin Loilome
    • 1
  1. 1.Department of Biochemistry, Liver Fluke and Cholangiocarcinoma Research Center, Faculty of MedicineKhon Kaen UniversityKhon KaenThailand
  2. 2.Center for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical ScienceKhon Kaen UniversityKhon KaenThailand
  3. 3.Department of Surgery, Liver Fluke and Cholangiocarcinoma Research Center, Faculty of MedicineKhon Kaen UniversityKhon KaenThailand
  4. 4.Department of Pathology and Liver Fluke and Cholangiocarcinoma Research Center, Faculty of MedicineKhon Kaen UniversityKhon KaenThailand

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