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Methods: Mouse mammary tumor cells were implanted under the dorsal skin flap over the calvaria and into a subcutaneous (subQ) lesions in female mice, generating tumors in the bone and subQ micro-Es. After implantation of the tumor cells, mice were treated with a TGF-β R1 kinase inhibitor (R1-Ki). Results: Treatment with R1-Ki decreased tumor volume and cell proliferation in the bone micro-E, but not in the subQ micro-E. R1-Ki treatment did not affect the induction of necrosis or apoptosis in either bone or subQ micro-E. The number of cells positive for the CSC markers, SOX2, and CD166 in the bone micro-E, were significantly higher than those in the subQ micro-E. R1-Ki treatment significantly decreased the number of CSC marker positive cells in the bone micro-E but not in the subQ micro-E. TGF-β activation of the MAPK/ERK and AKT pathways was the underlying mechanism of cell proliferation in the bone micro-E. BMP signaling did not play a role in cell proliferation in either micro-E. 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The Effects of TGF-β Signaling on Cancer Cells and Cancer Stem Cells in the Bone Microenvironment
http://hdl.handle.net/10069/39510
http://hdl.handle.net/10069/39510fcb7cb71-dd02-4f10-891d-da17f9000017
名前 / ファイル | ライセンス | アクション |
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IJMS20_5117.pdf (1.8 MB)
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Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2019-11-01 | |||||
タイトル | ||||||
タイトル | The Effects of TGF-β Signaling on Cancer Cells and Cancer Stem Cells in the Bone Microenvironment | |||||
言語 | ||||||
言語 | eng | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Bone metastasis | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Bone microenvironment | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Cancer stem cell | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Mammary tumor | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Non CSC | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | TGF-β | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
資源タイプ | journal article | |||||
著者 |
Futakuchi, Mitsuru
× Futakuchi, Mitsuru× Lami, Kris× Tachibana, Yuri× Yamamoto, Yukari× Furukawa, Masahiro× Fukuoka, Junya |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | Background: Transforming growth factor-β (TGF-β) plays a key role in bone metastasis formation; we hypothesized the possible involvement of TGF-β in the induction of cancer stem cells (CSCs) in the bone microenvironment (micro-E), which may be responsible for chemo-resistance. Methods: Mouse mammary tumor cells were implanted under the dorsal skin flap over the calvaria and into a subcutaneous (subQ) lesions in female mice, generating tumors in the bone and subQ micro-Es. After implantation of the tumor cells, mice were treated with a TGF-β R1 kinase inhibitor (R1-Ki). Results: Treatment with R1-Ki decreased tumor volume and cell proliferation in the bone micro-E, but not in the subQ micro-E. R1-Ki treatment did not affect the induction of necrosis or apoptosis in either bone or subQ micro-E. The number of cells positive for the CSC markers, SOX2, and CD166 in the bone micro-E, were significantly higher than those in the subQ micro-E. R1-Ki treatment significantly decreased the number of CSC marker positive cells in the bone micro-E but not in the subQ micro-E. TGF-β activation of the MAPK/ERK and AKT pathways was the underlying mechanism of cell proliferation in the bone micro-E. BMP signaling did not play a role in cell proliferation in either micro-E. Conclusion: Our results indicated that the bone micro-E is a key niche for CSC generation, and TGF-β signaling has important roles in generating CSCs and tumor cell proliferation in the bone micro-E. Therefore, it is critically important to evaluate responses to chemotherapeutic agents on both cancer stem cells and proliferating tumor cells in different tumor microenvironments in vivo. | |||||
書誌情報 |
International Journal of Molecular Sciences 巻 20, 号 20, p. 5117, 発行日 2019-10-15 |
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出版者 | ||||||
出版者 | MDPI | |||||
ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 16616596 | |||||
EISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 14220067 | |||||
DOI | ||||||
関連タイプ | isIdenticalTo | |||||
識別子タイプ | DOI | |||||
関連識別子 | 10.3390/ijms20205117 | |||||
権利 | ||||||
権利情報 | c 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). | |||||
著者版フラグ | ||||||
出版タイプ | VoR | |||||
出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||
引用 | ||||||
内容記述タイプ | Other | |||||
内容記述 | International Journal of Molecular Sciences, 20(20), art.no.5117; 2019 |