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Oncostatin M renders epithelial cell adhesion molecule-positive liver cancer stem cells sensitive to 5-fluorouracil by inducing hepatocytic differentiation

フォーマット:
論文
責任表示:
Yamashita, Taro ; Honda, Masao ; Nio, Kouki ; Nakamoto, Yasunari ; Yamashita, Tatsuya ; Takamura, Hiroyuki ; Tani, Takashi ; Zen, Yoh ; Kaneko, Shuichi
言語:
英語
出版情報:
American Association for Cancer Research, 2010-06-01
著者名:
Yamashita, Taro
Honda, Masao
Nio, Kouki
Nakamoto, Yasunari
Yamashita, Tatsuya
Takamura, Hiroyuki
Tani, Takashi
Zen, Yoh
Kaneko, Shuichi
続きを見る
掲載情報:
Cancer Research
ISSN:
0008-5472  CiNii Articles  Webcat Plus  JAIRO
巻:
70
通号:
11
開始ページ:
4687
終了ページ:
4697
バージョン:
author
概要:
金沢大学附属病院消化器内科<br />Recent evidence suggests that a certain type of hepatocellular carcinoma (HCC) is hierarchically organized by a subset of cells with stem cell features (cancer stem cells; CSC). Although normal stem cells and CSCs a re considered to share similar self-renewal programs, it remains unclear whether differentiation programs are also maintained in CSCs and effectively used for tumor eradication. In this study, we investigated the effect of oncostatin M (OSM), an interleukin 6-related cytokine known to induce the differentiation of hepatoblasts into hepatocytes, on liver CSCs. OSM receptor expression was detected in the majority of epithelial cell adhesion molecule-positive (EpCAM+) HCC with stem/progenitor cell features. OSM treatment resulted in the induction of hepatocytic differentiation of EpCAM+ HCC cells by inducing signal transducer and activator of transcription 3 activation, as determined by a decrease in stemness-related gene expression, a decrease in EpCAM, α-fetoprotein and cytokeratin 19 protein expressions, and an increase in albumin protein expression. OSM-treated EpCAM+ HCC cells showed enhanced cell proliferation with expansion of the EpCAM-negative non-CSC population. Noticeably, combination of OSM treatment with the chemotherapeutic agent 5-fluorouracil (5-FU), which eradicates EpCAM-negative non-CSCs, dramatically increased the number of apoptotic cells in vitro and suppressed tumor growth in vivo compared with either saline control, OSM, or 5-FU treatment alone. Taken together, our data suggest that OSM could be effectively used for the differentiation and active cell division of dormant EpCAM+ liver CSCs, and the combination of OSM and conventional chemotherapy with 5-FU efficiently eliminates HCC by targeting both CSCs and non-CSCs. ©2010 AACR. 続きを見る
URL:
http://hdl.handle.net/2297/24560

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