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Digestive Diseases and Sciences

, Volume 58, Issue 6, pp 1627–1635 | Cite as

A High Level of Integrin α6 Expression in Human Intrahepatic Cholangiocarcinoma Cells Is Associated with a Migratory and Invasive Phenotype

  • Yan-bing Ding
  • Bin Deng
  • You-sheng Huang
  • Wei-ming Xiao
  • Jian Wu
  • Yan-qing Zhang
  • Yuan-zhi Wang
  • Da-cheng Wu
  • Guo-tao Lu
  • Ke-yan Wu
Original Article

Abstract

Background

The integrin α6 subunit is part of the integrin α6β1 and α6β4 complexes, which are known to mediate the invasion of carcinoma cells. However, the precise role of integrin α6 in intrahepatic cholangiocarcinoma (ICC) has not yet been addressed.

Methods

Twenty cases of ICCs and matched nontumor samples were used to analyze integrin α6 expression by immunohistochemistry. After the expression of integrin α6 was determined by RT-PCR and Western blot in ICC cells, we regulated the expression of integrin α6 in ICC cells with specific vshRNA-integrin α6, and assessed the role of integrin α6 in the proliferation and metastasis/invasion of ICC cells. Finally, the involved mechanisms and clinical significance were further investigated.

Results

The expression of integrin α6 in ICC tissues was much higher than that in nontumor samples, and the high level of integrin α6 was detected in ICC cells compared with normal liver cells and HepG2 cells. After the down-regulation of integrin α6 in HCCC-9810 cells, we showed that the ability of ICC cells to metastasize and invade was much decreased in vitro, and cell proliferation was inhibited significantly. Further study indicated high expression of integrin α6 enhanced the activation of ERK1/2 and AKT signals in ICC cells and the inhibition of ERK1/2 down-regulated ICC cell proliferation, while the inhibition of AKT markedly impaired ICC cell metastasis and invasion. Integrin α6 overexpression was significantly correlated with larger tumors, multiple nodular, microvascular/bile duct invasion, and lymphatic metastasis (p < 0.05). The postoperative 5-year overall survival (OS) rate in patients with integrin α6low was higher than that of the integrin α6high group.

Conclusions

Overexpression of integrin α6 is associated with a migratory and invasive phenotype of ICC, and integrin α6 may be used as molecular target for therapy of ICC.

Keywords

ICC Integrin α6 Progression Mechanism 

Abbreviations

ICC

Intrahepatic cholangiocarcinoma

PLC

Primary liver cancer

IHC

Immunohistochemistry

ECM

Extracellular matrix

DMEM

Dulbecco’s modified Eagle’s medium

GAPDH

Glyceraldehyde-3-phosphate dehydrogenase

H&E

Hematoxylin and eosin

HCC

Hepatocellular carcinoma

RNAi

RNA interference

shRNA

Short hairpin RNA

ERK

Extracellular regulated protein kinase

PKB

Protein kinase B

PI3 K

Phosphatidylinositol-3-kinase

RT-PCR

Reverse transcription polymerase chain reaction

Notes

Acknowledgments

This work was supported by the National Natural Science Foundation of China (81260321) and the National Natural Science Foundation of Hainan Province (No. 811206).

Conflict of interest

None.

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Yan-bing Ding
    • 1
  • Bin Deng
    • 1
  • You-sheng Huang
    • 2
  • Wei-ming Xiao
    • 1
  • Jian Wu
    • 1
  • Yan-qing Zhang
    • 3
  • Yuan-zhi Wang
    • 1
  • Da-cheng Wu
    • 1
  • Guo-tao Lu
    • 1
  • Ke-yan Wu
    • 1
  1. 1.Department of GastroenterologyYangzhou No. 1 People’s Hospital, The Second Clinical School of Yangzhou UniversityYangzhouPeople’s Republic of China
  2. 2.Department of PathologyHainan Medical UniversityHaikouPeople’s Republic of China
  3. 3.The Medical College of Yangzhou UniversityYangzhouPeople’s Republic of China

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