title: Silencing of CXCR4 inhibits tumor cell proliferation and neural invasion in human hilar cholangiocarcinoma.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Emergency, Xiangya Hospital, Central-South University, Changsha, China.
authors.forename: Xin-Yu
authors.initials: XY
authors.lastname: Tan
authors.affiliation: Department of General Surgery, Xiangya Hospital, Central-South University, Changsha, China.
authors.forename: Shi
authors.initials: S
authors.lastname: Chang
authors.affiliation: Department of Intensive Care Unit, Xiangya Hospital, Central-South University, Changsha, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of General Surgery, Xiangya Hospital, Central-South University, Changsha, China.
authors.forename: Hui-Huan
authors.initials: HH
authors.lastname: Tang
mesh_terms: D000368:Aged; D001650:Bile Duct Neoplasms / Q000378:metabolism / Q000473:pathology*; D001653:Bile Ducts, Intrahepatic / Q000378:metabolism / Q000473:pathology*; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018281:Cholangiocarcinoma / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000378:metabolism / Q000473:pathology; D034622:RNA Interference / Q000502:physiology*; D034741:RNA, Small Interfering / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D034741:RNA, Small Interfering; D019718:Receptors, CXCR4
keywords: CXCR4; Hilar cholangiocarcinoma; Neural invasion; RNA interference