Metastin inhibits migration and invasion of renal cell carcinoma with overexpression of metastin receptor

Eur Urol. 2009 Feb;55(2):441-9. doi: 10.1016/j.eururo.2008.02.048. Epub 2008 Mar 11.


Background: Metastin, the final peptide of the KiSS-1 gene, has been proposed to suppress cell motility.

Objective: This study investigated whether renal cell carcinoma (RCC) tissue expresses metastin or its receptor, and clarified whether metastin can suppress migration and/or invasion and/or proliferation of RCC cells in vitro.

Design, setting, and participants: Twenty-five RCC samples were submitted. Fresh RCC tissues were prepared for real-time RT-PCR, and formalin-fixed and paraffin-embedded tissues blocks were examined by immunohistochemistry. RCC cell lines Caki-1 and ACHN were supplied for cell migration, invasion, and proliferation assays.

Measurements: Real-time RT-PCR was performed by using Taq Man gene expression system. ENVISION system was used in immunohistochemistry. Wound-healing assay and matrigel assays were used to identify migration and invasion abilities of RCC cell lines. Cell Counting Kit-8 was applied to measure the cell proliferation. Cell morphology was examined under a META system. Statistical analysis was performed with SPSS15.0J.

Results and limitations: In twenty-five RCC samples, the mRNA level of metastin receptor was identified to be significantly higher than non-neoplastic renal cortex by real-time RT-PCR (p=0.011). Immunohistochemical study also detected metastin receptor protein in all RCC tumors. In vitro, this study showed that metastin inhibited migration and invasion of Caki-1 and ACHN cells. In contrast, it had no effects on cell proliferation. Metastin (10 micromol/l) induced excessive formation of focal adhesions and stress fibers in Caki-1 and ACHN cells; this phenomenon was inhibited by pretreating pharmacological Rho-kinase inhibitor (Y-27632) to those cells.

Conclusion: This is the first report regarding overexpression of the metastin receptor hOT7T175 in human RCC. We demonstrate that metastin can inhibit migration and invasion of the RCC cell line, which is regulated by a Rho-kinase inhibitor. Metastin and its receptor are therefore probable targets for suppressing RCC.

MeSH terms

  • Carcinoma, Renal Cell / genetics
  • Carcinoma, Renal Cell / pathology*
  • Carcinoma, Renal Cell / surgery
  • Cell Adhesion
  • Cell Division
  • Cell Line, Tumor
  • Cell Movement
  • DNA Primers
  • Female
  • Genes, Tumor Suppressor
  • Humans
  • Immunohistochemistry
  • Kidney Neoplasms / genetics
  • Kidney Neoplasms / pathology*
  • Kidney Neoplasms / surgery
  • Kisspeptins
  • Male
  • Neoplasm Invasiveness
  • RNA, Messenger / genetics*
  • Receptors, G-Protein-Coupled / genetics*
  • Receptors, Kisspeptin-1
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / therapeutic use*


  • DNA Primers
  • KISS1 protein, human
  • KISS1R protein, human
  • Kisspeptins
  • RNA, Messenger
  • Receptors, G-Protein-Coupled
  • Receptors, Kisspeptin-1
  • Tumor Suppressor Proteins