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

Luminita Paraoan, Donna Gray, Paul Hiscott, Marta Garcia-Finana, Brian Lane, Bertil Damato, Ian Grierson

Research output: Contribution to journalArticle (journal)peer-review

23 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2504-13
Number of pages10
JournalFrontiers in Bioscience - Landmark
Volume14
Issue number7
DOIs
Publication statusPublished - 1 Jan 2009
Externally publishedYes

Keywords

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

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