Optimized Dosing Schedule Based on Circadian Dynamics of Mouse Breast Cancer Stem Cells Improves the Antitumor Effects of Aldehyde Dehydrogenase Inhibitor
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- Naoya Matsunaga
- 1Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan.
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- Takashi Ogino
- 1Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan.
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- Yukinori Hara
- 1Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan.
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- Takahiro Tanaka
- 1Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan.
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- Satoru Koyanagi
- 1Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan.
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- Shigehiro Ohdo
- 1Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan.
書誌事項
- 公開日
- 2018-07-01
- 資源種別
- journal article
- DOI
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- 10.1158/0008-5472.can-17-4034
- 公開者
- American Association for Cancer Research (AACR)
この論文をさがす
説明
<jats:title>Abstract</jats:title> <jats:p>Although malignant phenotypes of triple-negative breast cancer (TNBC) are subject to circadian alterations, the role of cancer stem cells (CSC) in defining this circadian change remains unclear. CSC are often characterized by high aldehyde dehydrogenase (ALDH) activity, which is associated with the malignancy of cancer cells and is used for identification and isolation of CSC. Here, we show that the population of ALDH-positive cells in a mouse 4T1 breast tumor model exhibits pronounced circadian alterations. Alterations in the number of ALDH-positive cells were generated by time-dependent increases and decreases in the expression of Aldh3a1. Importantly, circadian clock genes were rhythmically expressed in ALDH-negative cells, but not in ALDH-positive cells. Circadian expression of Aldh3a1 in ALDH-positive cells was dependent on the time-dependent release of Wingless-type mmtv integration site family 10a (WNT10a) from ALDH-negative cells. Furthermore, antitumor and antimetastatic effects of ALDH inhibitor N,N-diethylaminobenzaldehyde were enhanced by administration at the time of day when ALDH activity was increased in 4T1 tumor cells. Our findings reveal a new role for the circadian clock within the tumor microenvironment in regulating the circadian dynamics of CSC. These results should enable the development of novel therapeutic strategies for treatment of TNBC with ALDH inhibitors.</jats:p> <jats:p>Significance: This seminal report reveals that circadian dynamics of CSC are regulated by the tumor microenvironment and provides a proof of principle of its implication for chronotherapy in TNBC. Cancer Res; 78(13); 3698–708. ©2018 AACR.</jats:p>
収録刊行物
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- Cancer Research
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Cancer Research 78 (13), 3698-3708, 2018-07-01
American Association for Cancer Research (AACR)
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キーワード
- Mice, Inbred BALB C
- Nerve Tissue Proteins
- Triple Negative Breast Neoplasms
- Aldehyde Dehydrogenase
- Drug Administration Schedule
- Wnt Proteins
- Disease Models, Animal
- Mice
- Treatment Outcome
- Benzaldehydes
- Cell Line, Tumor
- Circadian Clocks
- Neoplastic Stem Cells
- Tumor Microenvironment
- Animals
- Humans
- Female
詳細情報 詳細情報について
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- CRID
- 1360004236367339648
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- ISSN
- 15387445
- 00085472
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- PubMed
- 29735553
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- 資料種別
- journal article
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- データソース種別
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- Crossref
- KAKEN
- OpenAIRE
