Cathepsin S and its inhibitor cystatin C: imbalance in uveal melanoma

Front Biosci (Landmark Ed). 2009 Jan 1;14:2504-13. doi: 10.2741/3393.


The present study aimed to investigate, as a follow-up of microarray profiling, the expression of the lysosomal cysteine protease cathepsin S and that of its endogenous inhibitor cystatin C in the most common primary intraocular tumor in adults, uveal melanoma. The expression pattern unveiled was characterized by a relative increase in the active form of the elastolytic and collagenolytic cathepsin S that was not counterbalanced by the expression of its strongest endogenous inhibitor cystatin C in the aggressive, highly metastatic uveal melanomas. The study provides evidence for a novel correlation between a specific cysteine protease activity and the strongest predictive factor for metastatic behavior in primary uveal melanoma and documents the first investigation of both a specific protease activity and its endogenous inhibitor in uveal melanoma. The results indicate that the shift in the balance between cathepsin S and cystatin C may be part of deregulated proteolytic pathways contributing to the invasive phenotype of uveal melanoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Blotting, Western
  • Cathepsins / antagonists & inhibitors
  • Cathepsins / metabolism*
  • Cystatin C / pharmacology*
  • Cysteine Proteinase Inhibitors / pharmacology*
  • Female
  • Humans
  • Immunohistochemistry
  • Male
  • Melanoma / enzymology*
  • Middle Aged
  • Uveal Neoplasms / enzymology*


  • Cystatin C
  • Cysteine Proteinase Inhibitors
  • Cathepsins
  • cathepsin S