Cargando…

Tumor necrosis factor-α promotes the lymphangiogenesis of gallbladder carcinoma through nuclear factor-κB-mediated upregulation of vascular endothelial growth factor-C

Vascular endothelial growth factor (VEGF)-C is an important lymphangiogenic factor involved in the lymphangiogenesis of gallbladder carcinoma (GBC) and the lymph node metastasis of the tumor. Tumor necrosis factor (TNF)-α, a key inflammatory cytokine responding to chronic inflammation of GBC, has be...

Descripción completa

Detalles Bibliográficos
Autores principales: Du, Qiang, Jiang, Lei, Wang, Xiaoqian, Wang, Meiping, She, Feifei, Chen, Yanling
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BlackWell Publishing Ltd 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4462363/
https://www.ncbi.nlm.nih.gov/pubmed/25154789
http://dx.doi.org/10.1111/cas.12504
_version_ 1782375640649957376
author Du, Qiang
Jiang, Lei
Wang, Xiaoqian
Wang, Meiping
She, Feifei
Chen, Yanling
author_facet Du, Qiang
Jiang, Lei
Wang, Xiaoqian
Wang, Meiping
She, Feifei
Chen, Yanling
author_sort Du, Qiang
collection PubMed
description Vascular endothelial growth factor (VEGF)-C is an important lymphangiogenic factor involved in the lymphangiogenesis of gallbladder carcinoma (GBC) and the lymph node metastasis of the tumor. Tumor necrosis factor (TNF)-α, a key inflammatory cytokine responding to chronic inflammation of GBC, has been reported to stimulate the expression of VEGF-C in some nonneoplastic cells. But whether TNF-α promotes the expression of VEGF-C in GBC has yet to be determined. Therefore, in the present study, the concentration of TNF-α and VEGF-C and the lymphatic vessel density (LVD) in the clinical GBC specimens were analyzed, and a linear correlation was found between the concentration of TNF-α and that of VEGF-C, the lymphatic vessel density (LVD); The transcription and protein level of VEGF-C in NOZ cell line were detected by real-time polymerase chain reaction (PCR) and enzyme linked immunosorbent assay (ELISA), and TNF-α enhanced the expression of VEGF-C in NOZ cell lines in a dose and time-dependent manner. Lymphatic tube formation in vitro was observed in a three-dimensional coculture system consisting of HDLECs and NOZ cell lines, and lymphatic vessels of GBC in nude mice model was detected by immunohistochemistry. TNF-α promoted the tube formation of lymphatic endothelial cells in vitro and the lymphangiogenesis of GBC in nude mice; The nuclear factor (NF)-κB binding site on the VEGF-C promoter was identified using Site-directed mutagenesis, electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation assay (ChIP). Taken together, TNF-α can upregulate the expression of VEGF-C and promote the lymphangiogenesis of GBC via NF-κB combining with the promoter of VEGF-C.
format Online
Article
Text
id pubmed-4462363
institution National Center for Biotechnology Information
language English
publishDate 2014
publisher BlackWell Publishing Ltd
record_format MEDLINE/PubMed
spelling pubmed-44623632015-10-05 Tumor necrosis factor-α promotes the lymphangiogenesis of gallbladder carcinoma through nuclear factor-κB-mediated upregulation of vascular endothelial growth factor-C Du, Qiang Jiang, Lei Wang, Xiaoqian Wang, Meiping She, Feifei Chen, Yanling Cancer Sci Original Articles Vascular endothelial growth factor (VEGF)-C is an important lymphangiogenic factor involved in the lymphangiogenesis of gallbladder carcinoma (GBC) and the lymph node metastasis of the tumor. Tumor necrosis factor (TNF)-α, a key inflammatory cytokine responding to chronic inflammation of GBC, has been reported to stimulate the expression of VEGF-C in some nonneoplastic cells. But whether TNF-α promotes the expression of VEGF-C in GBC has yet to be determined. Therefore, in the present study, the concentration of TNF-α and VEGF-C and the lymphatic vessel density (LVD) in the clinical GBC specimens were analyzed, and a linear correlation was found between the concentration of TNF-α and that of VEGF-C, the lymphatic vessel density (LVD); The transcription and protein level of VEGF-C in NOZ cell line were detected by real-time polymerase chain reaction (PCR) and enzyme linked immunosorbent assay (ELISA), and TNF-α enhanced the expression of VEGF-C in NOZ cell lines in a dose and time-dependent manner. Lymphatic tube formation in vitro was observed in a three-dimensional coculture system consisting of HDLECs and NOZ cell lines, and lymphatic vessels of GBC in nude mice model was detected by immunohistochemistry. TNF-α promoted the tube formation of lymphatic endothelial cells in vitro and the lymphangiogenesis of GBC in nude mice; The nuclear factor (NF)-κB binding site on the VEGF-C promoter was identified using Site-directed mutagenesis, electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation assay (ChIP). Taken together, TNF-α can upregulate the expression of VEGF-C and promote the lymphangiogenesis of GBC via NF-κB combining with the promoter of VEGF-C. BlackWell Publishing Ltd 2014-10 2014-10-09 /pmc/articles/PMC4462363/ /pubmed/25154789 http://dx.doi.org/10.1111/cas.12504 Text en © 2014 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association. http://creativecommons.org/licenses/by-nc-nd/3.0/ This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Original Articles
Du, Qiang
Jiang, Lei
Wang, Xiaoqian
Wang, Meiping
She, Feifei
Chen, Yanling
Tumor necrosis factor-α promotes the lymphangiogenesis of gallbladder carcinoma through nuclear factor-κB-mediated upregulation of vascular endothelial growth factor-C
title Tumor necrosis factor-α promotes the lymphangiogenesis of gallbladder carcinoma through nuclear factor-κB-mediated upregulation of vascular endothelial growth factor-C
title_full Tumor necrosis factor-α promotes the lymphangiogenesis of gallbladder carcinoma through nuclear factor-κB-mediated upregulation of vascular endothelial growth factor-C
title_fullStr Tumor necrosis factor-α promotes the lymphangiogenesis of gallbladder carcinoma through nuclear factor-κB-mediated upregulation of vascular endothelial growth factor-C
title_full_unstemmed Tumor necrosis factor-α promotes the lymphangiogenesis of gallbladder carcinoma through nuclear factor-κB-mediated upregulation of vascular endothelial growth factor-C
title_short Tumor necrosis factor-α promotes the lymphangiogenesis of gallbladder carcinoma through nuclear factor-κB-mediated upregulation of vascular endothelial growth factor-C
title_sort tumor necrosis factor-α promotes the lymphangiogenesis of gallbladder carcinoma through nuclear factor-κb-mediated upregulation of vascular endothelial growth factor-c
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4462363/
https://www.ncbi.nlm.nih.gov/pubmed/25154789
http://dx.doi.org/10.1111/cas.12504
work_keys_str_mv AT duqiang tumornecrosisfactorapromotesthelymphangiogenesisofgallbladdercarcinomathroughnuclearfactorkbmediatedupregulationofvascularendothelialgrowthfactorc
AT jianglei tumornecrosisfactorapromotesthelymphangiogenesisofgallbladdercarcinomathroughnuclearfactorkbmediatedupregulationofvascularendothelialgrowthfactorc
AT wangxiaoqian tumornecrosisfactorapromotesthelymphangiogenesisofgallbladdercarcinomathroughnuclearfactorkbmediatedupregulationofvascularendothelialgrowthfactorc
AT wangmeiping tumornecrosisfactorapromotesthelymphangiogenesisofgallbladdercarcinomathroughnuclearfactorkbmediatedupregulationofvascularendothelialgrowthfactorc
AT shefeifei tumornecrosisfactorapromotesthelymphangiogenesisofgallbladdercarcinomathroughnuclearfactorkbmediatedupregulationofvascularendothelialgrowthfactorc
AT chenyanling tumornecrosisfactorapromotesthelymphangiogenesisofgallbladdercarcinomathroughnuclearfactorkbmediatedupregulationofvascularendothelialgrowthfactorc