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 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.
Hori
A
A
Pharmaceutical Discovery Research Division, Takeda Chemical Industries, Ltd., Osaka, Japan. Hori_Akira@takeda.co.jp
Honda
S
S
Asada
M
M
Ohtaki
T
T
Oda
K
K
Watanabe
T
T
Shintani
Y
Y
Yamada
T
T
Suenaga
M
M
Kitada
C
C
Onda
H
H
Kurokawa
T
T
Nishimura
O
O
Fujino
M
M
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D016466:CHO Cells; D002118:Calcium / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement; D002478:Cells, Cultured; D002633:Chemotaxis / Q000187:drug effects; D006224:Cricetinae; D018076:DNA, Complementary / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli / Q000378:metabolism; D006801:Humans; D059648:Kisspeptins; D008024:Ligands; D010455:Peptides / Q000737:chemistry; D011506:Proteins / Q000494:pharmacology*; D011956:Receptors, Cell Surface / Q000737:chemistry* / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled; D000074502:Receptors, Kisspeptin-1; D018013:Receptors, Neuropeptide; D013997:Time Factors; D014162:Transfection; D025521:Tumor Suppressor Proteins; D014945:Wound Healing
D000970:Antineoplastic Agents; D018076:DNA, Complementary; C106628:KISS1 protein, human; C118688:KISS1R protein, human; D059648:Kisspeptins; D008024:Ligands; D010455:Peptides; D011506:Proteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D000074502:Receptors, Kisspeptin-1; D018013:Receptors, Neuropeptide; D025521:Tumor Suppressor Proteins; D002118:Calcium