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Tumor necrosis factor‐α promotes the lymphangiogenesis of gallbladder carcinoma through nuclear factor‐κB‐mediated upregulation of vascular endothelial growth factor‐C
| Content Provider | Scilit |
|---|---|
| Author | Du, Qiang Jiang, Lei Wang, Xiaoqian Wang, Meiping She, Feifei Chen, Yanling |
| Copyright Year | 2014 |
| Description | Journal: Cancer Science 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. |
| Related Links | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4462363/pdf |
| Ending Page | 1271 |
| Page Count | 11 |
| Starting Page | 1261 |
| e-ISSN | 13497006 |
| DOI | 10.1111/cas.12504 |
| Journal | Cancer Science |
| Issue Number | 10 |
| Volume Number | 105 |
| Language | English |
| Publisher | Wiley-Blackwell |
| Publisher Date | 2014-10-09 |
| Access Restriction | Open |
| Subject Keyword | Journal: Cancer Science Biotechnology and Microbiology Gallbladder Carcinoma Lymphangiogenesis Nculear Factor-κb Tumor Necrosis Factor-α Vascular Endothelial Growth Factor-c |
| Content Type | Text |
| Resource Type | Article |
