Open Access
Cathepsin S and its inhibitor cystatin C: imbalance in uveal melanoma
Luminita Paraoan1,Donna Gray1,Paul Hiscott1,Marta Garcia-Finana1,Brian Lane1,Bertil Damato1,Ian Grierson1
Unit of Ophthalmology, School of Clinical Science, University of Liverpool, Liverpool, UK.
DOI: 10.2741/3393 Volume 14 Issue 7, pp.2504-2513
Published: 01 January 2009
(This article belongs to the Special Issue Cystatins in health and disease)

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.

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Luminita Paraoan, Donna Gray, Paul Hiscott, Marta Garcia-Finana, Brian Lane, Bertil Damato, Ian Grierson. Cathepsin S and its inhibitor cystatin C: imbalance in uveal melanoma. Frontiers in Bioscience-Landmark. 2009. 14(7); 2504-2513.