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

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...

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Autores principales: Tatsumi, Yoshihiro, Miyake, Makito, Shimada, Keiji, Fujii, Tomomi, Hori, Shunta, Morizawa, Yosuke, Nakai, Yasushi, Anai, Satoshi, Tanaka, Nobumichi, Konishi, Noboru, Fujimoto, Kiyohide
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7313018/
https://www.ncbi.nlm.nih.gov/pubmed/32471161
http://dx.doi.org/10.3390/ijms21113789
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author Tatsumi, Yoshihiro
Miyake, Makito
Shimada, Keiji
Fujii, Tomomi
Hori, Shunta
Morizawa, Yosuke
Nakai, Yasushi
Anai, Satoshi
Tanaka, Nobumichi
Konishi, Noboru
Fujimoto, Kiyohide
author_facet Tatsumi, Yoshihiro
Miyake, Makito
Shimada, Keiji
Fujii, Tomomi
Hori, Shunta
Morizawa, Yosuke
Nakai, Yasushi
Anai, Satoshi
Tanaka, Nobumichi
Konishi, Noboru
Fujimoto, Kiyohide
author_sort Tatsumi, Yoshihiro
collection PubMed
description 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.
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spelling pubmed-73130182020-06-29 Inhibition of Heparanase Expression Results in Suppression of Invasion, Migration and Adhesion Abilities of Bladder Cancer Cells Tatsumi, Yoshihiro Miyake, Makito Shimada, Keiji Fujii, Tomomi Hori, Shunta Morizawa, Yosuke Nakai, Yasushi Anai, Satoshi Tanaka, Nobumichi Konishi, Noboru Fujimoto, Kiyohide Int J Mol Sci Article 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. MDPI 2020-05-27 /pmc/articles/PMC7313018/ /pubmed/32471161 http://dx.doi.org/10.3390/ijms21113789 Text en © 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/).
spellingShingle Article
Tatsumi, Yoshihiro
Miyake, Makito
Shimada, Keiji
Fujii, Tomomi
Hori, Shunta
Morizawa, Yosuke
Nakai, Yasushi
Anai, Satoshi
Tanaka, Nobumichi
Konishi, Noboru
Fujimoto, Kiyohide
Inhibition of Heparanase Expression Results in Suppression of Invasion, Migration and Adhesion Abilities of Bladder Cancer Cells
title Inhibition of Heparanase Expression Results in Suppression of Invasion, Migration and Adhesion Abilities of Bladder Cancer Cells
title_full Inhibition of Heparanase Expression Results in Suppression of Invasion, Migration and Adhesion Abilities of Bladder Cancer Cells
title_fullStr Inhibition of Heparanase Expression Results in Suppression of Invasion, Migration and Adhesion Abilities of Bladder Cancer Cells
title_full_unstemmed Inhibition of Heparanase Expression Results in Suppression of Invasion, Migration and Adhesion Abilities of Bladder Cancer Cells
title_short Inhibition of Heparanase Expression Results in Suppression of Invasion, Migration and Adhesion Abilities of Bladder Cancer Cells
title_sort inhibition of heparanase expression results in suppression of invasion, migration and adhesion abilities of bladder cancer cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7313018/
https://www.ncbi.nlm.nih.gov/pubmed/32471161
http://dx.doi.org/10.3390/ijms21113789
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