Gut Liver.  2014 Mar;8(2):196-204.

Silencing of CXCR4 Inhibits Tumor Cell Proliferation and Neural Invasion in Human Hilar Cholangiocarcinoma

• Tan XY
• Chang S
• Liu W
• Tang HH

Abstract

BACKGROUND/AIMS
To evaluate the expression of CXC motif chemokine receptor 4 (CXCR4) in the tissues of patients with hilar cholangiocarcinoma (hilar-CCA) and to investigate the cell proliferation and frequency of neural invasion (NI) influenced by RNAi-mediated CXCR4 silencing.
METHODS
An immunohistochemical technique was used to detect the expression of CXCR4 in 41 clinical tissues, including hilar-CCA, cholangitis, and normal bile duct tissues. The effects of small interference RNA (siRNA)-mediated CXCR4 silencing were detected in the hilar-CCA cell line QBC939. Cell proliferation was determined by MTT. Expression of CXCR4 was monitored by quantitative real time polymerase chain reaction and Western blot analysis. The NI ability of hilar-CCA cells was evaluated using a perineural cell and hilar-CCA cell coculture migration assay.
RESULTS
The expression of CXCR4 was significantly induced in clinical hilar-CCA tissue. There was a positive correlation between the expression of CXCR4 and lymph node metastasis/NI in hilar-CCA patients (p<0.05). Silencing of CXCR4 in tumor cell lines by siRNA led to significantly decreased NI (p<0.05) and slightly decreased cell proliferation.
CONCLUSIONS
CXCR4 is likely correlated with clinical recurrence of hilar-CCA. CXCR4 is involved in the invasion and proliferation of human hilar-CCA cell line QBC939, indicating that CXCR4 could be a promising therapeutic target for hilar-CCA.

Keyword

Hilar cholangiocarcinoma; Neural invasion; CXCR4; RNA interference

MeSH Terms

Aged
Bile Duct Neoplasms/metabolism/*pathology
Bile Ducts, Intrahepatic/metabolism/*pathology
Case-Control Studies
Cell Line, Tumor
Cell Proliferation
Cholangiocarcinoma/metabolism/*pathology
Female
Humans
Immunohistochemistry
Male
Middle Aged
Neoplasm Invasiveness
Neoplasm Recurrence, Local/metabolism/pathology
RNA Interference/*physiology
RNA, Small Interfering/metabolism
Receptors, CXCR4/antagonists & inhibitors/*metabolism
Tumor Cells, Cultured
RNA, Small Interfering
Receptors, CXCR4