Expression of cathepsin S and its inhibitor stefin A in sinonasal inverted papilloma

Abstract

Background: Dysregulation of cysteinyl cathepsins and their inhibitors, cystatins (stefins), were implied in progression of tumorgenesis; nevertheless, their role in sinonasal inverted papilloma (IP) is still unrecognized. Methods: The differential expression of cathepsins and stefins in IP and normal tissues were revealed by data of human Affymetrix U133A gene chips, real-time polymerase chain reaction (PCR) and immunohistochemistry. Results: Among the cathepsins and stefins family, expression of cathepsin S and stefin A were most differentially expressed (down- and up-regulated, respectively) in IP tissue as compared with normal tissues. Their expression levels were validated by real-time PCR, which showed the expression level of cathepsin S was significantly down-regulated, whereas the expression of stefin A was significantly up-regulated in IP tissue compared to normal sinus mucosa. Using immunohistochemistry, expression of cathepsin S was observed in stromal and epithelial area macrophages of normal sinus mucosa, but no obvious expression of cathepsin S was found in IP tissue. In contrast, over-expression of stefin A was present in nearly all layers of the proliferative squamous cells of IP, but expression of stefin A was only detected in a scattered area of normal sinus mucosa. Conclusion: Down-regulation of cathepsin S and up-regulation of its endogenous inhibitor, stefin A, were found in IP tissues as compared with their expression level in normal sinus mucosa tissues. The biological significance of inverse expression of both stefin A and cathepsin S in sinonasal IP need further investigation in the future.