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Decreased expression of kallikrein-related peptidase 13: Possible contribution to metastasis of human oral cancer

Authors

  • Shunsaku Ishige,

    1. Department of Clinical Molecular Biology, Graduate School of Medicine, Chiba University, Chiba, Japan
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  • Atsushi Kasamatsu,

    1. Department of Clinical Molecular Biology, Graduate School of Medicine, Chiba University, Chiba, Japan
    2. Department of Dentistry and Oral-Maxillofacial Surgery, Chiba University Hospital, Chiba, Japan
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  • Kenji Ogoshi,

    1. Department of Clinical Molecular Biology, Graduate School of Medicine, Chiba University, Chiba, Japan
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  • Yasuhiro Saito,

    1. Department of Clinical Molecular Biology, Graduate School of Medicine, Chiba University, Chiba, Japan
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  • Katsuya Usukura,

    1. Department of Clinical Molecular Biology, Graduate School of Medicine, Chiba University, Chiba, Japan
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  • Hidetaka Yokoe,

    1. Department of Oral and Maxillofacial Surgery Research Insutitute, National Defense Medical College Hospital, Tokorozawa, Japan
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  • Yukinao Kouzu,

    1. Department of Clinical Molecular Biology, Graduate School of Medicine, Chiba University, Chiba, Japan
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  • Hirofumi Koike,

    1. Department of Clinical Molecular Biology, Graduate School of Medicine, Chiba University, Chiba, Japan
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  • Yosuke Sakamoto,

    1. Department of Dentistry and Oral-Maxillofacial Surgery, Chiba University Hospital, Chiba, Japan
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  • Katsunori Ogawara,

    1. Department of Clinical Molecular Biology, Graduate School of Medicine, Chiba University, Chiba, Japan
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  • Masashi Shiiba,

    1. Department of Clinical Molecular Biology, Graduate School of Medicine, Chiba University, Chiba, Japan
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  • Hideki Tanzawa,

    1. Department of Clinical Molecular Biology, Graduate School of Medicine, Chiba University, Chiba, Japan
    2. Department of Dentistry and Oral-Maxillofacial Surgery, Chiba University Hospital, Chiba, Japan
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  • Katsuhiro Uzawa

    Corresponding author
    1. Department of Clinical Molecular Biology, Graduate School of Medicine, Chiba University, Chiba, Japan
    2. Department of Dentistry and Oral-Maxillofacial Surgery, Chiba University Hospital, Chiba, Japan
    • Department of Clinical Molecular Biology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.

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Abstract

The human kallikrein-related peptidase family is comprised of 15 serine protease genes on chromosome 19q13.4 [1]. Our previous microarray analyses showed that the gene kallikrein-related peptidase 13 (KLK13) was down-regulated in oral squamous cell carcinoma (OSCC) cell lines. We evaluated the expression status of KLK13 in primary OSCCs and performed functional molecular experiments in OSCC cell lines. In 102 primary tumors studied, KLK13 expression significantly (P < 0.05) decreased compared with matched normal counterparts. Interestingly, KLK13-negative cases correlated significantly (P < 0.05) with regional lymph node metastasis. In vitro, cells overexpressing KLK13 (oeKLK13) had decreased invasiveness and motility and up-regulation of adhesion molecules (E-cadherin, α-catenin, β-catenin, junction plakoglobin, plakophilin4, desmocollin2, desmoglein3, and desmoplakin) compared with control cells. A rescue experiment that transfected oeKLK13 cells with siRNA against KLK13 restored invasiveness and migration activities with down-regulated adhesion molecules. Based on our results, we concluded that KLK13 may play an important role in regulating cellular migration and invasiveness, making the loss of KLK13 a potential biomarker for early detection of lymph node metastasis in OSCCs. © 2013 Wiley Periodicals, Inc.

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