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CD44v9 Induces Stem Cell-Like Phenotypes in Human Cholangiocarcinoma
http://hdl.handle.net/10076/00020071
http://hdl.handle.net/10076/00020071d4b3f479-d0e3-4d47-8372-f3078d77f84c
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
2021DM0912 (3.5 MB)
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| Item type | 学位論文 / Thesis or Dissertation(1) | |||||||
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| 公開日 | 2022-01-04 | |||||||
| タイトル | ||||||||
| タイトル | CD44v9 Induces Stem Cell-Like Phenotypes in Human Cholangiocarcinoma | |||||||
| 言語 | en | |||||||
| 言語 | ||||||||
| 言語 | eng | |||||||
| キーワード | ||||||||
| 言語 | en | |||||||
| 主題Scheme | Other | |||||||
| 主題 | cholangiocarcinoma | |||||||
| キーワード | ||||||||
| 言語 | en | |||||||
| 主題Scheme | Other | |||||||
| 主題 | CD44 variant 9 | |||||||
| キーワード | ||||||||
| 言語 | en | |||||||
| 主題Scheme | Other | |||||||
| 主題 | epithelial-mesenchymal transition | |||||||
| キーワード | ||||||||
| 言語 | en | |||||||
| 主題Scheme | Other | |||||||
| 主題 | Wnt/β-catenin | |||||||
| キーワード | ||||||||
| 言語 | en | |||||||
| 主題Scheme | Other | |||||||
| 主題 | cancer stem cell | |||||||
| 資源タイプ | ||||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_db06 | |||||||
| 資源タイプ | doctoral thesis | |||||||
| アクセス権 | ||||||||
| アクセス権 | open access | |||||||
| アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||||
| 著者 |
SUWANNAKUL, NATTAWAN
× SUWANNAKUL, NATTAWAN
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| 著者（ヨミ） | ||||||||
| 姓名 | スワナクル, ナタワン | |||||||
| 言語 | ja | |||||||
| 抄録 | ||||||||
| 内容記述タイプ | Abstract | |||||||
| 内容記述 | Background: Our previous study demonstrated an overexpression of CD44 variant9 (CD44v9) in human cholangiocarcinoma (CCA) tissues that was associated with inflammation-related tumor development. However, the participation of CD44v9 in cholangiocarcinogenesis remains poorly understood. Therefore, in this study, we examined the potential roles of CD44v9 in CCA cells to understand the carcinogenic mechanism. Methods: Using normal cholangiocytes (MMNK1) and CCA cells (KKU213), the expression levels of CD44v9 and its related molecules were quantified through RT-qPCR and immunofluorescence (IF) staining. To evaluate its biological functions, we performed CD44v9 (exon 13) silencing using siRNA transfection, and assessed cell proliferation through MTT assay, cell migration and invasion by transwell technique, and carried out cell cycle analysis by flow cytometry. In vivo tumor growth was assessed by nude mouse xenografts, and histological and molecular changes were determined. Results: KKU213 exhibited higher protein expression levels of CD44v9 than those of MMNK1 through IF staining. RT-qPCR analysis revealed that the mRNA expression level of CD44v9 was predominantly elevated in CCA cells along with its neighboring exons such as variant 8 and 10, minimally affecting the standard form of CD44. CD44v9 silencing could regulate redox system in CCA cells by reducing the expression levels of SOD3 and cysteine transporter xCT. CD44v9 silencing suppressed the CCA cell proliferation by induction of apoptosis and cell cycle arrest. Migration and invasion were decreased in CD44v9 siRNA-treated CCA cells. CD44v9 downregulation inhibited CCA tumor growth in mouse xenografts. IF analysis demonstrated the histological changes in xenograft tissues such as an increase in connective tissues through collagen deposition and reduction of hyaluronic acid synthesis through CD44v9 silencing. CD44v9 knockdown in vitro and in vivo increased E-cadherin and reduced vimentin expression levels, resulting in reduction of epithelial-mesenchymal transition (EMT) process. Moreover, CD44v9 modulated Wnt10a and β-catenin in tumorigenesis. Conclusion: Our results indicate that CD44v9 plays a potential role in CCA development by the regulation of cell proliferation and redox balancing. CD44v9 silencing may suppress tumor growth, migration and invasion through EMT: a finding that could potentially be applied in the development of targeted cancer therapy. |
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| 言語 | en | |||||||
| 内容記述 | ||||||||
| 内容記述タイプ | Other | |||||||
| 内容記述 | 本文/Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Tsu, Japan | |||||||
| 内容記述 | ||||||||
| 内容記述タイプ | Other | |||||||
| 内容記述 | 15p | |||||||
| 書誌情報 |
発行日 2021-09-15 |
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| DOI | ||||||||
| 識別子タイプ | DOI | |||||||
| 関連識別子 | 10.3389/fcell.2020.00417 | |||||||
| フォーマット | ||||||||
| 内容記述タイプ | Other | |||||||
| 内容記述 | application/pdf | |||||||
| 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 | |||||||
| 出版者 | ||||||||
| 出版者 | 三重大学 | |||||||
| 出版者（ヨミ） | ||||||||
| 値 | ミエダイガク | |||||||
| 学位名 | ||||||||
| 学位名 | 博士(医学) | |||||||
| 学位授与機関 | ||||||||
| 学位授与機関識別子Scheme | kakenhi | |||||||
| 学位授与機関識別子 | 14101 | |||||||
| 学位授与機関名 | 三重大学 | |||||||
| 学位授与年月日 | ||||||||
| 学位授与年月日 | 2021-09-15 | |||||||
| 学位授与番号 | ||||||||
| 学位授与番号 | 甲医学第2087号 | |||||||
| ノート | ||||||||
| 値 | Frontiers in Cell and Developmental Biology, 3;8:417に掲載 | |||||||
| 資源タイプ（三重大） | ||||||||
| 値 | Doctoral Dissertation / 博士論文 | |||||||
