Inhibition of Heparanase Expression Results in Suppression of Invasion, Migration and Adhesion Abilities of Bladder Cancer Cells.

• Material Type: 博士論文
• Title: Inhibition of Heparanase Expression Results in Suppression of Invasion, Migration and Adhesion Abilities of Bladder Cancer Cells.
• Author/Editor: Tatsumi, Yoshihiro; Miyake, Makito; Shimada, Keiji; Fujii, Tomomi; Hori, Shunta; Morizawa, Yosuke; Nakai, Yasushi; Anai, Satoshi; Tanaka, Nobumichi; Konishi, Noboru; Fujimoto, Kiyohide
• Author Heading: Tatsumi, Yoshihiro; Miyake, Makito; Shimada, Keiji; Fujii, Tomomi; Hori, Shunta; Morizawa, Yosuke; Nakai, Yasushi; Anai, Satoshi; Tanaka, Nobumichi; Konishi, Noboru; Fujimoto, Kiyohide
• Publication, Distribution, etc.: MDPI
• Publication Date: 2020-05-27
• Publication Date (W3CDTF): 2020-05-27
• Alternative Title: 膀胱癌細胞株において、ヘパラナーゼを阻害することにより、細胞浸潤、遊走、接着能を抑制する
• Periodical title: International journal of molecular sciences
• No. or year of volume/issue: 21 11
• Volume: 21
• Issue: 11
• Pages: Article No.3789-
• ISSN (Periodical Title): ISSN : 1422-0067
• Degree grantor/type: 奈良県立医科大学
• Date Granted: 2021-03-15
• Dissertation Number: 乙第1506号
• Degree Type: 博士（医学）
• Text Language Code: eng
• Subject Heading: heparanase; syndecan-1; heparan sulfate proteoglycans (HSPGs); urothelial carcinoma
• Target Audience: 一般
• Note (General): type:Thesis; Heparan sulfate proteoglycan syndecan-1, CD138, is known to be associated with cell proliferation, adhesion, and migration in malignancies. We previously reported that syndecan-1 (CD138) may contribute to urothelial carcinoma cell survival and progression. We investigated the role of heparanase, an enzyme activated by syndecan-1 in human urothelial carcinoma. Using human urothelial cancer cell lines, MGH-U3 and T24, heparanase expression was reduced with siRNA and RK-682, a heparanase inhibitor, to examine changes in cell proliferation activity, induction of apoptosis, invasion ability of cells, and its relationship to autophagy. A bladder cancer development mouse model was treated with RK-682 and the bladder tissues were examined using immunohistochemical analysis for Ki-67, E-cadherin, LC3, and CD31 expressions. Heparanase inhibition suppressed cellular growth by approximately 40% and induced apoptosis. The heparanase inhibitor decreased cell activity in a concentration-dependent manner and suppressed invasion ability by 40%. Inhibition of heparanase was found to suppress autophagy. In N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)-induced bladder cancer mice, treatment with heparanase inhibitor suppressed the progression of cancer by 40%, compared to controls. Immunohistochemistry analysis showed that heparanase inhibitor suppressed cell growth, and autophagy. In conclusion, heparanase suppresses apoptosis and promotes invasion and autophagy in urothelial cancer.; 博士（医学）・乙第1506号・令和3年3月15日; © 2020 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/).; identifier:International journal of molecular sciences Vol.21 No.11 Article No.3789 (2020 May); identifier:14220067; identifier:http://ginmu.naramed-u.ac.jp/dspace/handle/10564/3932; identifier:International journal of molecular sciences, 21(11): Article No.3789
• Source: fulltext; http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3932/1/01%e4%b9%991506%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdf; http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3932/2/02%e4%b9%991506%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdf; http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3932/3/03%e4%b9%991506%e6%9c%ac%e6%96%87.pdf
• Access Restrictions: インターネット公開
• Related Material (DOI): 10.3390/ijms21113789
• Periodical Title (NCID): AA12038549; https://ci.nii.ac.jp/ncid/AA12038549
• Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）; https://irdb.nii.ac.jp
• Original Data Provider (Database): 奈良県立医科大学 : 奈良県立医科大学機関リポジトリ GINMU