title: Over-expression of nerve growth factor-β in human cholangiocarcinoma QBC939 cells promote tumor progression.
abstract: OBJECTIVE
  It has been shown that nerve growth factor-β (NGF-β) promoted the initiation and progression of many tumors, and we have previously demonstrated that the expression of NGF-β was associated with tumor stage, nerve infiltration and lymph node metastasis in human hilar cholangiocarcinoma. However, whether NGF-β promotes tumor progression in human cholangiocarcinoma requires further investigation. Therefore, we aimed to determine the effects of NGF-β on the progression of human cholangiocarcinoma.
  
  
  METHODS
  Human cholangiocarcinoma QBC939 stable cell lines with over-expressed or silenced NGF-β genes were generated with pEGFP-N1-NGF-β and pGPU6/GFP/Neo-NGF-β-shRNA recombinant plasmids. Cell proliferation assay, colony formation assay, cell cycle analysis, apoptosis assay and tumorigenicity assay were performed to evaluate the role of NGF-β in the progression of human cholangiocarcinoma. In addition, human lymphatic endothelial cells were co-cultured with QBC939 culture supernatants, and the cell proliferation and migration abilities of the lymphatic endothelial cells were evaluated.
  
  
  RESULTS
  Forced expression of NGF-β in QBC939 cell lines promoted proliferation, colony formation and tumorigenicity in these cells and inhibited the apoptosis. However, down-regulation of NGF-β inhibited proliferation, colony formation and tumorigenicity, and increased the apoptotic rate of QBC939 cells. In addition, the NGF-β gain-of-function induced a high expression of vascular endothelial growth factor C and enhanced the proliferation and migration of lymphatic endothelial cells, while NGF-β loss-of-function showed opposite effects.
  
  
  CONCLUSIONS
  We concluded that NGF-β promoted tumor progression in human cholangiocarcinoma QBC939 cells. Our results provided a new concept to understand the role of NGF-β in cholangiocarcinoma progression, and might provide important information for the development of new targeted therapies in human cholangiocarcinoma.
authors: Department of Hepato-Pancreato-Biliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong Province, China.
authors: Xiu-Jing
authors: XJ
authors: Yue
authors: Lei-Bo
authors: LB
authors: Xu
authors: Man-Sheng
authors: MS
authors: Zhu
authors: Rui
authors: R
authors: Zhang
authors: Chao
authors: C
authors: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D018281:Cholangiocarcinoma / Q000235:genetics* / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D023061:Gene Order; D020868:Gene Silencing; D064593:Heterografts; D006801:Humans; D051379:Mice; D020932:Nerve Growth Factor / Q000235:genetics*; D047368:Tumor Burden / Q000235:genetics; D042582:Vascular Endothelial Growth Factor C / Q000235:genetics
chemical_list: D042582:Vascular Endothelial Growth Factor C; D020932:Nerve Growth Factor
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