Metastin suppresses the motility and growth of CHO Cells transfected with its receptor

We recently reported having identified of the ligand for an orphan G-protei n-coupled receptor, hOT7T175, as the gene product (68-121)-amide of the met astasis 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 pulmon ary metastasis of hOT7T174-transfected B16-BL6 melanomas in vivo. In the pr esent 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-term inally truncated peptides, metastin(40-54) and metastin(45-54) inhibited th e 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 t hat metastin is a potent inhibitor of cell motility,. leading to suppressio n of cell growth and antimetastatic activity, and suggest that low molecula r chemical compounds could replace its activity as a novel antimetastatic a gent. (C) 2001 Academic Press.