CD44v9 Induces Stem Cell-Like Phenotypes in Human Cholangiocarcinoma

• 資料種別: 博士論文
• タイトル: CD44v9 Induces Stem Cell-Like Phenotypes in Human Cholangiocarcinoma
• 著者・編者: SUWANNAKUL, NATTAWAN
• 著者標目: SUWANNAKUL, NATTAWAN
• 出版事項: 三重大学
• 出版年月日等: 2021-09-15
• 出版年（W3CDTF）: 2021-09-15
• 授与機関名: 三重大学
• 授与年月日: 2021-09-15
• 授与年月日（W3CDTF）: 2021-09-15
• 報告番号: 甲医学第2087号
• 学位: 博士(医学)
• 博論授与番号: 甲医学第2087号
• 本文の言語コード: eng
• 件名標目: cholangiocarcinoma; CD44 variant 9; epithelial-mesenchymal transition; Wnt/β-catenin; cancer stem cell
• 対象利用者: 一般
• 一般注記: application/pdf; 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.; 本文/Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Tsu, Japan; 15p
• DOI: info:doi/10.3389/fcell.2020.00417; https://doi.org/info:doi/10.3389/fcell.2020.00417
• 国立国会図書館永続的識別子: info:ndljp/pid/11976676; https://dl.ndl.go.jp/pid/11976676
• コレクション（共通）: 障害者向け資料
• コレクション（障害者向け資料：レベル1）: テキストデータ
• コレクション（個別）: 国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文; https://dl.ndl.go.jp/collections/A00014
• 収集根拠: 博士論文（自動収集）
• 受理日（W3CDTF）: 2022-01-10T16:22:37+09:00
• 作成日（W3CDTF）: 2022-01-04
• 記録形式（IMT）: application/pdf
• オンライン閲覧公開範囲: 国立国会図書館内限定公開
• デジタル化資料送信: 図書館・個人送信対象外
• 遠隔複写可否（NDL）: 可
• 掲載誌（URI）: http://hdl.handle.net/10076/00020071; https://mie-u.repo.nii.ac.jp/records/14453
• 連携機関・データベース: 国立国会図書館 : 国立国会図書館デジタルコレクション; https://dl.ndl.go.jp