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.
Paraoan
Luminita
L
Unit of Ophthalmology, School of Clinical Science, University of Liverpool, Liverpool, UK. luminita.paraoan@liverpool.ac.uk
Gray
Donna
D
Hiscott
Paul
P
Garcia-Finana
Marta
M
Lane
Brian
B
Damato
Bertil
B
Grierson
Ian
I
D000368:Aged; D015153:Blotting, Western; D002403:Cathepsins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D055316:Cystatin C / Q000494:pharmacology*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008545:Melanoma / Q000201:enzymology*; D008875:Middle Aged; D014604:Uveal Neoplasms / Q000201:enzymology*
D055316:Cystatin C; D015853:Cysteine Proteinase Inhibitors; D002403:Cathepsins; C028217:cathepsin S