Metastasis suppressor gene KiSS-1 encodes peptide ligand of a G-protein-coupled receptor.
Ohtaki. T T; Shintani. Y Y; Honda. S S; Matsumoto. H H; Hori. A A; Kanehashi. K K; Terao. Y Y; Kumano. S S; Takatsu. Y Y; Masuda. Y Y; Ishibashi. Y Y; Watanabe. T T; Asada. M M; Yamada. T T; Suenaga. M M; Kitada. C C; Usuki. S S; Kurokawa. T T; Onda. H H; Nishimura. O O; Fujino. M M
Key Findings
- KiSS-1 encodes a 54‑amino‑acid, amidated peptide (metastin) that acts as the natural ligand for the orphan GPCR hOT7T175.
- Metastin reduces chemotaxis and invasion of cells engineered to express the receptor in vitro.
- In mice, metastin treatment lowered lung metastasis of melanoma cells that express the receptor.
Practical Outcomes
- The study shows a potential new way to block cancer spread, but it does not provide any dosage, protocol, or immediate health‑boosting application for biohackers or the general public. At present it remains a pre‑clinical finding with future therapeutic promise rather than a usable strategy.
Summary
Researchers discovered that the KiSS-1 gene makes a small peptide called metastin that can bind to a specific cell‑surface receptor and slow down the spread of cancer cells in lab tests and mouse experiments.
Abstract
Metastasis is a major cause of death in cancer patients and involves a multistep process including detachment of cancer cells from a primary cancer, invasion of surrounding tissue, spread through circulation, re-invasion and proliferation in distant organs. KiSS-1 is a human metastasis suppressor gene, that suppresses metastases of human melanomas and breast carcinomas without affecting tumorigenicity. However, its gene product and functional mechanisms have not been elucidated. Here we show that KiSS-1 (refs 1, 4) encodes a carboxy-terminally amidated peptide with 54 amino-acid residues, which we have isolated from human placenta as the endogenous ligand of an orphan G-protein-coupled receptor (hOT7T175) and have named 'metastin'. Metastin inhibits chemotaxis and invasion of hOT7T175-transfected CHO cells in vitro and attenuates pulmonary metastasis of hOT7T175-transfected B16-BL6 melanomas in vivo. The results suggest possible mechanisms of action for KiSS-1 and a potential new therapeutic approach.
Study Information
pubmed
2001
2001-05-31T00:00:00.000Z
10.1038/35079135
1409
36