In vivo imaging models of bone and brain metastases and pleural carcinomatosis with a novel human EML4-ALK lung cancer cell line

フォーマット:

論文

責任表示:

Nanjo, Shigeki ; Nakagawa, Takayuki ; Takeuchi, Shinji ; Kita, Kenji ; Fukuda, Koji ; Nakada, Mitsutoshi ; Uehara, Hisanori ; Nishihara, Hiroshi ; Hara, Eiji ; Uramoto, Hidetaka ; Tanaka, Fumihiro ; Yano, Seiji

言語:

英語

出版情報:

Japanese Cancer Association / Blackwell Publishing Ltd, 2015-03-01

著者名:

Nanjo, Shigeki

Nakagawa, Takayuki

Takeuchi, Shinji

Kita, Kenji

Fukuda, Koji

Nakada, Mitsutoshi

Uehara, Hisanori

Nishihara, Hiroshi

Hara, Eiji

Uramoto, Hidetaka

Tanaka, Fumihiro

Yano, Seiji

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掲載情報:

Cancer Science

ISSN:

1347-9032      

巻:

106

通号:

3

開始ページ:

244

終了ページ:

252

バージョン:

publisher

概要:

がん進展制御研究所<br />EML4-ALK lung cancer accounts for approximately 3-7% of non-small-cell lung cancer cases. To investigate the molecular mechanism underlying tumor progression and targeted drug sensitivity/resistance in EML4-ALK lung can … cer, clinically relevant animal models are indispensable. In this study, we found that the lung adenocarcinoma cell line A925L expresses an EML4-ALK gene fusion (variant 5a, E2:A20) and is sensitive to the ALK inhibitors crizotinib and alectinib. We further established highly tumorigenic A925LPE3 cells, which also have the EML4-ALK gene fusion (variant 5a) and are sensitive to ALK inhibitors. By using A925LPE3 cells with luciferase gene transfection, we established in vivo imaging models for pleural carcinomatosis, bone metastasis, and brain metastasis, all of which are significant clinical concerns of advanced EML4-ALK lung cancer. Interestingly, crizotinib caused tumors to shrink in the pleural carcinomatosis model, but not in bone and brain metastasis models, whereas alectinib showed remarkable efficacy in all three models, indicative of the clinical efficacy of these ALK inhibitors. Our in vivo imaging models of multiple organ sites may provide useful resources to analyze further the pathogenesis of EML4-ALK lung cancer and its response and resistance to ALK inhibitors in various organ microenvironments. © 2015 The Authors. 続きを見る

URL:

http://hdl.handle.net/2297/45961