論文 - 詳細
| RRC ID | 62101 |
|---|---|
| 著者 | Kawamoto M, Onishi H, Ozono K, Yamasaki A, Imaizumi A, Kamakura S, Nakano K, Oda Y, Sumimoto H, Nakamura M. |
| タイトル | Tropomyosin-related kinase B mediated signaling contributes to the induction of malignant phenotype of gallbladder cancer. |
| ジャーナル | Oncotarget |
| Abstract |
This study aims to demonstrate the clinical and biological significance of Brain derived neurotrophic factor (BDNF)/Tropomyosin-related kinase B (TrkB) signaling in gallbladder cancer (GBC) through a series of in vitro and in vivo experiments. TrkB expression was detected in 63 (91.3%) out of 69 surgically resected primary GBC specimens by immunohistochemistry. TrkB expression in the invasive front correlated with T factor (p=0.0391) and clinical staging (p=0.0391). Overall survival was lower in patients with high TrkB expression in the invasive front than in those with low TrkB expression (p=0.0363). In vitro experiment, we used five TrkB-expressing GBC cell lines with or without K-ras mutation. TrkB-mediated signaling increased proliferation and the invasiveness by inducing epithelial mesenchymal transition, and activating matrix metalloproteinases-2 (MMP-2) and MMP-9. Inhibition of TrkB-mediated signaling also decreased hypoxia-inducible factor-1α, vascular endothelial growth factor A (VEGF-A), VEGF-C, and VEGF-D expression. In vivo experiment, inhibition of TrkB-mediated signaling suppressed tumorigenicity and tumor growth in GBC. These findings demonstrate that TrkB-mediated signaling contributes to the induction of malignant phenotypes (proliferation, invasiveness, angiogenesis, lymphangiogenesis, and tumorigenesis) in GBC, and could be a promising therapeutic target regardless of K-ras mutation status. |
| 巻・号 | 8(22) |
| ページ | 36211-36224 |
| 公開日 | 2017-5-30 |
| DOI | 10.18632/oncotarget.16063 |
| PII | 16063 |
| PMID | 28423707 |
| PMC | PMC5482650 |
| MeSH | Aged Animals Brain-Derived Neurotrophic Factor / metabolism* Cell Line, Tumor Cell Movement Cell Proliferation Epithelial-Mesenchymal Transition Female Gallbladder Neoplasms / genetics* Gallbladder Neoplasms / mortality Gene Expression Regulation, Neoplastic Humans Hypoxia-Inducible Factor 1, alpha Subunit / metabolism Male Matrix Metalloproteinases / metabolism Membrane Glycoproteins / genetics* Membrane Glycoproteins / metabolism Mice Mice, Inbred BALB C Mice, Nude Neoplasm Staging RNA, Small Interfering / genetics Receptor, trkB / genetics* Receptor, trkB / metabolism Signal Transduction Survival Analysis Tumor Burden Vascular Endothelial Growth Factor A / metabolism |
| IF | 5.168 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 2 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | TGBC2TKB(RCB1130) |