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

被引:11
作者
Tatsumi, Yoshihiro [1 ,2 ]
Miyake, Makito [1 ]
Shimada, Keiji [2 ]
Fujii, Tomomi [2 ]
Hori, Shunta [1 ]
Morizawa, Yosuke [1 ]
Nakai, Yasushi [1 ]
Anai, Satoshi [1 ]
Tanaka, Nobumichi [1 ]
Konishi, Noboru [2 ]
Fujimoto, Kiyohide [1 ]
机构
[1] Nara Med Univ, Dept Urol, 840 Shijo Cho, Nara 6348522, Japan
[2] Nara Med Univ, Dept Pathol, 840 Shijo Cho, Nara 6348522, Japan
关键词
heparanase; syndecan-1; heparan sulfate proteoglycans (HSPGs); urothelial carcinoma; GROWTH IN-VIVO; TUMOR-GROWTH; MAMMALIAN HEPARANASE; SYNDECAN-1; PROGRESSION; METASTASIS; SULFATE; PROTEOGLYCANS; MOLECULE; PROTEIN;
D O I
10.3390/ijms21113789
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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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页数:12
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