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.
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.
Yoshioka
Kunihiko
K
Department of Urology, Tokyo Medical University. 6-7-1 Nishi-shinjuku, Shinjuku-ku, Tokyo, Japan. kunihiko@tokyo-med.ac.jp
Ohno
Yoshio
Y
Horiguchi
Yutaka
Y
Ozu
Choichiro
C
Namiki
Kazunori
K
Tachibana
Masaaki
M
D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002448:Cell Adhesion / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D005109:Extracellular Matrix / Q000378:metabolism; D016147:Genes, Tumor Suppressor; D006801:Humans; D059648:Kisspeptins; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D000074502:Receptors, Kisspeptin-1; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
C106628:KISS1 protein, human; C118688:KISS1R protein, human; D059648:Kisspeptins; D010455:Peptides; D043562:Receptors, G-Protein-Coupled; D000074502:Receptors, Kisspeptin-1; D025521:Tumor Suppressor Proteins; D020778:Matrix Metalloproteinase 2