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Please use this identifier to cite or link to this item: http://hdl.handle.net/10564/3932

Title: Inhibition of Heparanase Expression Results in Suppression of Invasion, Migration and Adhesion Abilities of Bladder Cancer Cells.
Other Titles: 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
Authors: Tatsumi, Yoshihiro
Miyake, Makito
Shimada, Keiji
Fujii, Tomomi
Hori, Shunta
Morizawa, Yosuke
Nakai, Yasushi
Anai, Satoshi
Tanaka, Nobumichi
Konishi, Noboru
Fujimoto, Kiyohide
Keywords: heparanase
heparan sulfate proteoglycans (HSPGs)
urothelial carcinoma
Issue Date: 27-May-2020
Publisher: MDPI
Citation: International journal of molecular sciences Vol.21 No.11 Article No.3789 (2020 May)
Abstract: 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.
Description: 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/).
URI: http://hdl.handle.net/10564/3932
ISSN: 14220067
Academic Degrees and number: 24601B1506
Degree-granting date: 2021-03-15
Degree name: 博士(医学)
Degree-granting institutions: 奈良県立医科大学
Appears in Collections:2020年度

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