Gelatinolytic Activity of Matrix Metalloproteinases 2 and 9 in Middle Ear Cholesteatoma

Background: Cholesteatoma of the middle ear or mastoid is a hyperproliferative disorder of keratinocytes characterized by a progressive bone erosion. Matrix metalloproteinase (MMP)-2 and MMP-9 gelatinases are endopeptidases targeting extracellular protein. Several studies examined the role of gelatinases in the pathogenesis of cholesteatoma, but the biologic mechanism by which cholesteatoma destroys the bone tissue remains unclear.

Objectives: The aim of this study was to characterize the activity of MMP-2 and MMP-9 in human cholesteatoma and external auditory canal skin.

Methods: In the study, specimens of cholesteatoma and middle ear canal skin from 14 patients treated surgically at the Department of Otolaryngology were used. After two-step extraction of MMP-2 and MMP-9 from tissue samples, gelatinolytic activity was assessed with zymography.

Results: We noticed the augmentation of MMP-9 (p = .0001) and MMP-2 (p = .046) activity obtained from cholesteatoma in comparison with control skin. The MMP-9 active to latent ratio was significantly higher in cholesteatoma samples versus normal skin.

Conclusion: The present study indicates that MMP-9 and, to a lesser degree, MMP-2 overexpression may be implicated in the molecular mechanisms of cholesteatoma invasion and bone destruction.