| 著者 |
木村, 翔一
WEKO
35124
| ja |
木村, 翔一
宮崎大学
|
| ja-Kana |
キムラ, ショウイチ
|
| en |
Kimura, Syoichi
Kimura, Shoichi
University of Miyazaki
|
Search repository
岩野, 智
WEKO
35018
e-Rad_Researcher
10734832
| ja |
岩野, 智
宮崎大学
|
| ja-Kana |
イワノ, サトシ
|
| en |
Iwano, Satoshi
University of Miyazaki
|
Search repository
秋岡, 貴弘
WEKO
33764
e-Rad_Researcher
60816940
| ja |
秋岡, 貴弘
宮崎大学
|
| ja-Kana |
アキオカ, タカヒロ
|
| en |
Akioka, Takahiro
University of Miyazaki
|
Search repository
Kuchimaru, Takahiro
川口, 真紀子
WEKO
9881
e-Rad_Researcher
90405598
| ja |
川口, 真紀子
宮崎大学
|
| ja-Kana |
カワグチ, マキコ
|
| en |
Kawaguchi, Makiko
University of Miyazaki
|
Search repository
福島, 剛
WEKO
9884
e-Rad_Researcher
10452913
| ja |
福島, 剛
宮崎大学
|
| ja-Kana |
フクシマ, ツヨシ
|
| en |
Fukushima, Tsuyoshi
University of Miyazaki
|
Search repository
佐藤, 勇一郎
WEKO
9417
e-Rad_Researcher
90347055
| ja |
佐藤, 勇一郎
宮崎大学
|
| ja-Kana |
サトウ, ユウイチロウ
|
| en |
Sato, Yuichiro
University of Miyazaki
|
Search repository
片岡, 寛章
WEKO
9886
e-Rad_Researcher
10214321
| ja |
片岡, 寛章
宮崎大学
|
| ja-Kana |
カタオカ, ヒロアキ
|
| en |
Kataoka, Hiroaki
University of Miyazaki
|
Search repository
賀本, 敏行
WEKO
9783
e-Rad_Researcher
00281098
| ja |
賀本, 敏行
宮崎大学
|
| ja-Kana |
カモト, トシユキ
|
| en |
Kamoto, Toshiyuki
University of Miyazaki
|
Search repository
向井, 尚一郎
WEKO
26958
| en |
Mukai, Shoichiro
University of Miyazaki
|
| ja |
向井, 尚一郎
宮崎大学
|
| ja-Kana |
ムカイ, ショウイチロウ
|
Search repository
澤田, 篤郎
WEKO
35206
e-Rad_Researcher
10784796
| ja |
澤田, 篤郎
宮崎大学
|
| ja-Kana |
サワダ, アツロウ
|
| en |
Sawada, Atsuro
University of Miyazaki
|
Search repository
|
|
内容記述 |
The liver is the most lethal metastatic site in castration-resistant prostate cancer (CRPC). Overexpression of MET protein has been reported in CRPC, and MET is an important driver gene in androgen-independent CRPC cells. Mouse CRPC cell line CRTC2 was established by subcutaneous injection of hormone-sensitive PC cells (TRAMP-C2) in castrated nude mice. CRCT2/luc2 cells were injected into the spleen of castrated nude mice, and liver metastasis was confirmed at 2 weeks post-injection. We administered MET inhibitor (MET-I) and HGF activator inhibitor (HGFA-I) to this liver metastasis model and assessed the therapeutic effect. After intrasplenic injection, CRTC2 showed a higher incidence of liver metastasis whereas no metastasis was observed in TRAMP-C2. Microarray analysis revealed increased expression of HGF, MET, and HPN, HGFAC (encoding HGF activating proteases) in liver metastasis. Proliferation of CRCT2 was significantly inhibited by co-administration of MET-I and HGFA-I by in vitro analysis with HGF-enriched condition. In an analysis of the mouse model, the combination-therapy group showed the strongest reduction for liver metastasis. Immunohistochemical staining also revealed the strongest decrease in phosphorylation of MET in the combination-therapy group. Co-culture with HGF-expressed mouse fibroblasts showed attenuation of the inhibitory effect of MET-I; however, additional HGFA-I overcame the resistance. We established an androgen-independent CRPC cell line, CRTC2, and liver metastasis model in mice. Significant effect was confirmed by combined treatment of MET-I and HGFA-I by in vitro and in vivo analysis. The results suggested the importance of combined treatment with both MET- and HGF-targeting agents in the treatment of HGF-enriched conditions including liver metastasis. |
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