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

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.