CCL5/CCR5 axis promotes the motility of human oral cancer cells

Authors

  • Jing-Yuan Chuang,

    1. Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung Taiwan
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  • Wei-Hung Yang,

    1. Department of Orthopaedic Surgery, China Medical University Beigang Hospital, Yun-Lin County, Taiwan
    2. School of Chinese Medicine, China Medical University, Taichung Taiwan
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  • Hsien-Te Chen,

    1. Department of Orthopaedics, China Medical University Hospital, Taichung, Taiwan
    2. Department of Materials Science and Engineering, Feng Chia University, Taichung, Taiwan
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  • Chun-Yin Huang,

    1. Department of Orthopaedic Surgery, China Medical University Beigang Hospital, Yun-Lin County, Taiwan
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  • Tzu-Wei Tan,

    1. Department of Pharmacology, China Medical University, Taichung Taiwan
    2. Graduate Institute of Basic Medical Science, China Medical University, Taichung Taiwan
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  • Yuh-Tzy Lin,

    1. Department of Nursing and Management, Jen-Teh Junior College of Medicine, Miaoli County, Taiwan
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  • Chin-Jung Hsu,

    1. School of Chinese Medicine, China Medical University, Taichung Taiwan
    2. Department of Orthopaedic Surgery, China Medical University Hospital, Taichung, Taiwan
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  • Yi-Chin Fong,

    1. School of Chinese Medicine, China Medical University, Taichung Taiwan
    2. Department of Orthopaedic Surgery, China Medical University Hospital, Taichung, Taiwan
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  • Chih-Hsin Tang

    Corresponding author
    1. Department of Pharmacology, China Medical University, Taichung Taiwan
    2. Graduate Institute of Basic Medical Science, China Medical University, Taichung Taiwan
    • Department of Pharmacology, College of Medicine, China Medical University, No. 91, Hsueh-Shih Road, Taichung, Taiwan.
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  • C.-Y. Chuang, W.-H. Yang, and H.-T. Chen contributed equally to this study.

Abstract

CCL5 (previously called RANTES) is in the CC-chemokine family and plays a crucial role in the migration and metastasis of human cancer cells. On the other hand, the effect of CCL5 is mediated via CCR receptor. RT-PCR and flow cytometry studies demonstrated CCR5 but not CCR1 and CCR3 mRNA in oral cancer cell lines, especially higher in those with high invasiveness (SCC4) as compared with lower levels in HSC3 cells and SCC9 cells. Stimulation of oral cancer cells with CCL5 directly increased the migration and metalloproteinase-9 (MMP-9) production. MMP-9 small interfering RNA inhibited the CCL5-induced MMP-9 expression and thereby significantly inhibited the CCL5-induced cell migration. Activations of phospholipase C (PLC), protein kinase Cδ (PKCδ), and NF-κB pathways after CCL5 treatment was demonstrated, and CCL5-induced expression of MMP-9 and migration activity was inhibited by the specific inhibitor of PLC, PKCδ, and NF-κB cascades. In addition, migration-prone sublines demonstrate that cells with increasing migration ability had more expression of MMP-9, CCL5, and CCR5. Taken together, these results indicate that CCL5/CCR5 axis enhanced migration of oral cancer cells through the increase of MMP-9 production. J. Cell. Physiol. 220: 418–426, 2009. © 2009 Wiley-Liss, Inc.

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