Relevance of A Disintegrin and Metalloproteinase Domain-Containing (ADAM)9 Protein Expression to Bladder Cancer Malignancy
Michika Moriwaki,
Trang Thi-Huynh Le,
Shian-Ying Sung,
Yura Jotatsu,
Youngmin Yang,
Yuto Hirata,
Aya Ishii,
Yi-Te Chiang,
Kuan-Chou Chen,
Katsumi Shigemura,
Masato Fujisawa
Affiliations
Michika Moriwaki
Department of International Health, Kobe University Graduate School of Health Sciences, 7-10-2 Tomogaoka, Suma-ku, Kobe 654-0142, Japan
Trang Thi-Huynh Le
International Ph.D. Program in Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan
Shian-Ying Sung
International Ph.D. Program for Translational Science, College of Medical Science and Technology, Taipei Medical University, 250 Wu-Hsing st, Taipei 11031 Taiwan
Yura Jotatsu
Department of International Health, Kobe University Graduate School of Health Sciences, 7-10-2 Tomogaoka, Suma-ku, Kobe 654-0142, Japan
Youngmin Yang
Department of Urology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan
Yuto Hirata
Department of International Health, Kobe University Graduate School of Health Sciences, 7-10-2 Tomogaoka, Suma-ku, Kobe 654-0142, Japan
Aya Ishii
Department of International Health, Kobe University Graduate School of Health Sciences, 7-10-2 Tomogaoka, Suma-ku, Kobe 654-0142, Japan
Yi-Te Chiang
Department of Urology, Taipei Medical University Shuang Ho Hospital, 291 Zhongzheng Road, Taipei 23561, Taiwan
Kuan-Chou Chen
Department of Urology, Taipei Medical University Shuang Ho Hospital, 291 Zhongzheng Road, Taipei 23561, Taiwan
Katsumi Shigemura
Department of International Health, Kobe University Graduate School of Health Sciences, 7-10-2 Tomogaoka, Suma-ku, Kobe 654-0142, Japan
Masato Fujisawa
Department of Urology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan
We evaluated the effect of A Disintegrin and Metalloproteinase Domain-Containing (ADAM)9 protein on exacerbation in bladder cancer KK47 and T24. First, we knocked down ADAM9 and investigated cell proliferation, migration, cell cycle, and the epithelial–mesenchymal transition (EMT)-related proteins expression in vitro. We then investigated the expression level of ADAM9 in clinical urine cytology samples and the Cancer Genome Atlas (TCGA) data. Cell proliferation was significantly reduced in both cell lines after ADAM9 knockdown. In the cell-cycle assay, the percentage of G0/G1 cells was significantly increased in ADAM9 knockdown T24. Migration of T24 was more strongly suppressed than KK47. The expression level of EMT-related proteins suggested that EMT was suppressed in ADAM9 knockdown T24. TCGA analysis revealed that ADAM9 mRNA expression was significantly higher in stage IV and high-grade cancer than in other stages and low-grade cancer. Moreover, in the gene expression omnibus (GEO) study, bladder cancer with surrounding carcinoma and invasive carcinoma showed significantly high ADAM9 mRNA expression. We found that ADAM9 knockdown suppressed cell proliferation and migration in bladder cancer and that high-grade bladder cancer is correlated with higher expression of ADAM9.
