A High Level of Integrin alpha 6 Expression in Human Intrahepatic Cholangiocarcinoma Cells Is Associated with a Migratory and Invasive Phenotype

• Published in: Digestive diseases and sciences 2013-06, Vol.58 (6), p.1627-1635
• Main Authors: Ding, Yan-bing, Deng, Bin, Huang, You-sheng, Xiao, Wei-ming, Wu, Jian, Zhang, Yan-qing, Wang, Yuan-zhi, Wu, Da-cheng, Lu, Guo-tao, Wu, Ke-yan
• Format: Article
• Language: English
• ISSN: 0163-2116; 1573-2568
• DOI: 10.1007/s10620-012-2524-6

Background: The integrin alpha 6 subunit is part of the integrin alpha 6 beta 1 and alpha 6 beta 4 complexes, which are known to mediate the invasion of carcinoma cells. However, the precise role of integrin alpha 6 in intrahepatic cholangiocarcinoma (ICC) has not yet been addressed. Methods: Twenty cases of ICCs and matched nontumor samples were used to analyze integrin alpha 6 expression by immunohistochemistry. After the expression of integrin alpha 6 was determined by RT-PCR and Western blot in ICC cells, we regulated the expression of integrin alpha 6 in ICC cells with specific vshRNA-integrin alpha 6, and assessed the role of integrin alpha 6 in the proliferation and metastasis/invasion of ICC cells. Finally, the involved mechanisms and clinical significance were further investigated. Results: The expression of integrin alpha 6 in ICC tissues was much higher than that in nontumor samples, and the high level of integrin alpha 6 was detected in ICC cells compared with normal liver cells and HepG2 cells. After the down-regulation of integrin alpha 6 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 alpha 6 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 alpha 6 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 alpha 6 super(low) was higher than that of the integrin alpha 6 super(high) group. Conclusions: Overexpression of integrin alpha 6 is associated with a migratory and invasive phenotype of ICC, and integrin alpha 6 may be used as molecular target for therapy of ICC.