Extracellular vesicles from senescent hepatic stellate cells promote cell viability of hepatoma cells through increasing EGF secretion from differentiated THP?1 cells

• Material Type: 博士論文
• ISSN: 2049-9434
• Title: Extracellular vesicles from senescent hepatic stellate cells promote cell viability of hepatoma cells through increasing EGF secretion from differentiated THP?1 cells
• Volume: 12 4
• Author/Editor: 宮副, 由梨
• Author Heading: 宮副, 由梨
• Publication, Distribution, etc.: Spandidos Publications
• Publication Date: 2020-09-02
• Publication Date (W3CDTF): 2020-09-02
• Alternative Title: 老化肝星細胞から分泌される細胞外小胞は、分化THP-1細胞からのEGF発現増加を介し肝癌細胞増殖能を促進させる
• Periodical title: Biomedical Reports
• Degree grantor/type: Nagasaki University (長崎大学)
• Date Granted: 2020-09-02
• Date Granted (W3CDTF): 2020-09-02
• Dissertation Number: 甲医歯薬第1274号
• Degree Type: 博士(医学)
• Conferring No. (Dissertation): 甲医歯薬第1274号
• Text Language Code: eng
• Subject Heading: epidermal growth factor; etoposide; extracellular vesicles; hepatic stellate cells; hepatocellular carcinoma; senescence?associated secretory phenotype
• Target Audience: 一般
• Note (General): Since the discovery of the senescence?associated secretory phenotype, the role of senescent hepatic stellate cells (HSCs) in hepatocellular carcinoma (HCC) development has gained increasing attention. Similar to cytokines, extracellular vesicles (EVs) are essential for intercellular communication. However, the function of EVs derived from senescent HSCs in HCC progression has not been extensively studied. The aims of the present study were to characterize the EVs derived from senescent HSCs and determine their role in the tumor microenvironment. Cellular senescence was induced in human hepatic stellate cells (HHSteCs) with various concentrations of etoposide. Induction was confirmed using EdU staining and 53BP1 and p21 immunostaining. EVs were isolated by ultracentrifugation and analyzed by nanoparticle tracking analysis. Multiplex immunoassays were used to compare the levels of growth factors secreted from hepatoma cell lines and macrophage cells pretreated with EVs derived from senescent HHSteCs (senescent EVs) with those pretreated with EVs derived from normal cultured HHSteCs (normal EVs). Treatment with 25 μM etoposide for 3 days was the most effective at inducing senescence in HHSteCs. This finding was confirmed by induction of irreversible cell?cycle arrest, upregulation of 53BP1 and p21 expression, and increased SA?β?gal staining. Senescent HHSteCs released increased quantities of EV particles compared with normally cultured HHSteCs. Multiplex analysis revealed that there was no difference between hepatoma cell lines treated with normal EVs and those treated with senescent EVs in growth factor secretion. In contrast, the secretion of epidermal growth factor (EGF) was increased by macrophage cells treated with senescent EVs compared with those treated with normal EVs. Furthermore, senescent EVs did not affect the viability of hepatoma cells but increased the viability of hepatoma cells co?cultured with macrophage cells. In conclusion, the release of EVs from senescent HSCs was higher compared with normal HSCs. Furthermore, senescent EVs promoted HCC development by upregulating EGF secretion from macrophages.; 長崎大学学位論文 学位記番号:博(医歯薬)甲第1274号 学位授与年月日:令和2年9月2日; Author: Yuri Miyazoe, Satoshi Miuma, Hisamitsu Miyaaki, Yasuko Kanda, Suguru Nakashiki, Ryu Sasaki, Masafumi Haraguchi, Hidetaka Shibata, Takuya Honda, Naota Taura, Kazuhiko Nakao; Citation: Biomedical Reports, 12(4), pp.163-170, 2020; identifier:Nagasaki University (長崎大学), 博士(医学) (2020-09-02); http://hdl.handle.net/10069/40345
• DOI: info:doi/10.3892/br.2020.1279; https://doi.org/info:doi/10.3892/br.2020.1279
• Persistent ID (NDL): info:ndljp/pid/11551967; https://dl.ndl.go.jp/pid/11551967
• Collection: 障害者向け資料
• Collection (Materials For Handicapped People:1): テキストデータ
• Collection (particular): 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
• Acquisition Basis: 博士論文（自動収集）
• Date Accepted (W3CDTF): 2020-10-06T21:18:06+09:00
• Date Created (W3CDTF): 2020-12-16
• Format (IMT): PDF
• Access Restrictions: 国立国会図書館内限定公開
• Service for the Digitized Contents Transmission Service: 図書館・個人送信対象外
• Availability of remote photoduplication service: 可
• Related Material (URI): http://hdl.handle.net/10069/40345
• Periodical Title (URI): http://hdl.handle.net/10069/40280
• Data Provider (Database): 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

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2021-03-07 再収集