Effects of a KiSS-1 peptide, a metastasis suppressor gene, on the invasive ability of renal cell carcinoma cells through a modulation of a matrix metalloproteinase 2 expression.
Yoshioka. Kunihiko K; Ohno. Yoshio Y; Horiguchi. Yutaka Y; Ozu. Choichiro C; Namiki. Kazunori K; Tachibana. Masaaki M
Key Findings
- Only one of four kidney cancer cell lines naturally expressed KiSS‑1, but all had the receptor hOT7T175.
- The metastin 45‑54 peptide sharply cut invasive ability and increased collagen‑4 attachment in KiSS‑1‑negative cells, but not in KiSS‑1‑positive cells.
- Metastin 45‑54 reduced both mRNA and protein levels of MMP‑2, a key enzyme for cell invasion.
Practical Outcomes
- The study is early‑stage lab work with no human data, dosing guidance, or safety info, so it doesn’t translate into any usable protocol for longevity, metabolism, or performance. Biohackers should view it as a mechanistic cancer‑research finding rather than a practical supplement or therapy.
Summary
A short piece of the KiSS-1 protein (called metastin 45‑54) was tested on kidney cancer cells in a dish and was found to make the cells less able to invade and move, mainly by lowering a molecule called MMP‑2 that helps cells break through tissue. This effect only showed up in cells that didn’t already make KiSS‑1 themselves.
Abstract
Although effects of a metastasis suppressor gene, KiSS-1, have been postulated to be mediated by its receptor, hOT7T175, the mechanism of such effects remains unknown. This study was designed to evaluate the mechanism of how KiSS-1 works and to assess effects of a synthesized truncated KiSS-1 protein on the invasive ability of renal cell carcinoma (RCC) cells. Four RCC cell lines, Caki-1, KU19-20, RSP and RSM, were investigated to determine mRNA expressions of KiSS-1, its receptor, hOT7T175, matrix metalloproteinases (MMPs) and MMP inhibitors. While all cell lines demonstrated hOT7T175 mRNA expressions, only Caki-1 had KiSS-1 transcripts. A synthesized truncated KiSS-1 peptide, metastin (45-54), produced a marked suppression of the invasive ability in KU19-20 cells, which were deficient for KiSS-1 transcripts, but not in Caki-1 cells. Metastin (45-54) also increased the ability of KU19-20 cells to attach to collagen 4. Both MMP-2 mRNA levels and protein production were significantly decreased only in KU19-20 cells by metastin (45-54). In conclusion, metastin (45-54) may have potential therapeutic use by suppressing the motility and invasive ability of RCC cells which possess hOT7T175 with either a negative expression or very low expression level of KiSS-1 through, at least in part, the down-regulation of MMP-2.
Study Information
pubmed
2008
2008-07-01T00:00:00.000Z
10.1016/j.lfs.2008.06.018
41
17