| 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
|
| リソース情報 |
| ヒト・動物細胞 |
TGBC2TKB(RCB1130) |
