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-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 ovar...

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Published in:Biochemical and biophysical research communications 2001-09, Vol.286 (5), p.958-963
Main Authors: Hori, Akira, Honda, Susumu, Asada, Mari, Ohtaki, Tetsuya, Oda, Katsuaki, Watanabe, Takuya, Shintani, Yasushi, Yamada, Takao, Suenaga, Masato, Kitada, Chieko, Onda, Haruo, Kurokawa, Tsutomu, Nishimura, Osamu, Fujino, Masahiko
Format: Article
Language:English
Subjects:
Animals
Antineoplastic Agents - pharmacology
Calcium - metabolism
Cell Division - drug effects
Cell Movement
Cells, Cultured
Chemotaxis - drug effects
CHO Cells
Cricetinae
DNA, Complementary - metabolism
Dose-Response Relationship, Drug
Escherichia coli - metabolism
Humans
KiSS-1
Kisspeptins
Ligands
metastin
motility
OT7T175
Peptides - chemistry
Proteins - pharmacology
Receptors, Cell Surface - chemistry
Receptors, Cell Surface - metabolism
Receptors, G-Protein-Coupled
Receptors, Kisspeptin-1
Receptors, Neuropeptide
Time Factors
Transfection
Tumor Suppressor Proteins
Wound Healing
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Summary: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.
ISSN:0006-291X
1090-2104
DOI:10.1006/bbrc.2001.5470