Over-expression of nerve growth factor-β in human cholangiocarcinoma QBC939 cells promote tumor progression.

AIMS: 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...

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Main Authors: Xiu-Jing Yue, Lei-Bo Xu, Man-Sheng Zhu, Rui Zhang, Chao Liu
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2013-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3634741?pdf=render
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author Xiu-Jing Yue
Lei-Bo Xu
Man-Sheng Zhu
Rui Zhang
Chao Liu
author_facet Xiu-Jing Yue
Lei-Bo Xu
Man-Sheng Zhu
Rui Zhang
Chao Liu
author_sort Xiu-Jing Yue
collection DOAJ
description AIMS: 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.
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spelling doaj.art-89c465295ed8404fb06bc11fee0d9b7d2022-12-22T00:07:29ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0184e6202410.1371/journal.pone.0062024Over-expression of nerve growth factor-β in human cholangiocarcinoma QBC939 cells promote tumor progression.Xiu-Jing YueLei-Bo XuMan-Sheng ZhuRui ZhangChao LiuAIMS: 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.http://europepmc.org/articles/PMC3634741?pdf=render
spellingShingle Xiu-Jing Yue
Lei-Bo Xu
Man-Sheng Zhu
Rui Zhang
Chao Liu
Over-expression of nerve growth factor-β in human cholangiocarcinoma QBC939 cells promote tumor progression.
PLoS ONE
title Over-expression of nerve growth factor-β in human cholangiocarcinoma QBC939 cells promote tumor progression.
title_full Over-expression of nerve growth factor-β in human cholangiocarcinoma QBC939 cells promote tumor progression.
title_fullStr Over-expression of nerve growth factor-β in human cholangiocarcinoma QBC939 cells promote tumor progression.
title_full_unstemmed Over-expression of nerve growth factor-β in human cholangiocarcinoma QBC939 cells promote tumor progression.
title_short Over-expression of nerve growth factor-β in human cholangiocarcinoma QBC939 cells promote tumor progression.
title_sort over expression of nerve growth factor β in human cholangiocarcinoma qbc939 cells promote tumor progression
url http://europepmc.org/articles/PMC3634741?pdf=render
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AT manshengzhu overexpressionofnervegrowthfactorbinhumancholangiocarcinomaqbc939cellspromotetumorprogression
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