Regular Article
Metastin Suppresses the Motility and Growth of CHO Cells Transfected with Its Receptor

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Abstract

We recently reported having identified of the ligand for an orphan G-protein-coupled receptor, hOT7T175, as the gene product (68–121)-amide of the metastasis suppressor gene KiSS-1. We further showed that the ligand, which we named “metastin,” inhibits chemotaxis and invasion of Chinese hamster ovary (CHO) cells transfected with hOT7T175 cDNA (CHO/h175) in vitro, and pulmonary metastasis of hOT7T175-transfected B16-BL6 melanomas in vivo. In the present study, we investigated the activity of metastin in CHO/h175 cells in greater detail. Metastin significantly suppressed motility in a chemotaxis assay and wound healing assay at 10–100 nM order concentrations. Two N-terminally truncated peptides, metastin(40–54) and metastin(45–54) inhibited the migration of CHO/h175 cells as potently as metastin itself. Metastin also inhibited the spreading, monolayer growth and colony formation in agar (0.8%) of CHO/h175 cells at 10–100 nM concentrations. These results indicate that metastin is a potent inhibitor of cell motility, leading to suppression of cell growth and antimetastatic activity, and suggest that low molecular chemical compounds could replace its activity as a novel antimetastatic agent.

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    Abbreviations used: CHO, Chinese hamster ovary; GPCR, G-protein-coupled receptor; FBS, fetal bovine serum; SRB, sulforhodamine B; MCP-1, monocyte chemoattractant protein 1; S1P, sphingosine 1-phosphate;LPA, lysophosphatidic acid.

    1

    To whom correspondence should be addressed at Pharmaceutical Research Division I, Takeda Chemical Industries, Ltd., Jusohonmachi, 2-17-85 Yodogawa-ku, Osaka 532-8686, Japan. Fax: 81 6 300 6306 or 81 6 300 6206. E-mail: [email protected].

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