Metastin suppresses the motility and growth of CHO Cells transfected with its receptor
Metastin suppresses the motility and growth of CHO Cells transfected with its receptor
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DOI：
10.1006/bbrc.2001.5470
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发表时间：
2001-09-07
影响因子：
3.1
通讯作者：
Fujino, M
中科院分区：
文献类型：
--
作者：
Hori, A;Honda, S;Fujino, M
我们最近报道了一种孤儿G蛋白偶联受体的配体hOT7T175，它是转移抑制基因KISS-1的基因产物(68-121)-酰胺。我们进一步证明了这种配体，我们命名为“Metastin”，在体外抑制了转hOT7T175基因的中国仓鼠卵巢(CHO)细胞(CHO/H175)的趋化和侵袭，并在体内抑制了转hOT7T174的B16-BL6黑色素瘤的肺转移。在本研究中，我们更详细地研究了Metastin在CHO/H175细胞中的活性。在10-100 nM的浓度范围内，Metastin显著抑制趋化试验和伤口愈合试验中的运动性。两个N端截短的多肽，Metastin(40-54)和Metastin(45-54)抑制CHO/H175细胞的迁移，与Metastin本身一样有效。在10-100 nM浓度范围内，Metastin还抑制CHO/H175细胞在琼脂(0.8%)上的铺展、单层生长和集落形成。这些结果表明，Metastin是一种有效的细胞运动抑制因子。抑制细胞生长和抗转移活性，提示小分子化合物可替代其作为一种新型的抗转移药物。(C)2001年学术出版社。
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 hOT7T174-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. (C) 2001 Academic Press.