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

Expression of cathepsin S and its inhibitor stefin A in sinonasal inverted papilloma
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DOI:
10.4193/rhino09.114
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发表时间:
2010-09-01
期刊:
影响因子:
7.2
通讯作者:
Tsai, C. -N.
Tsai, C. -N.
中科院分区:
医学1区
文献类型:
--
作者:
Huang, C. -C.;Lee, T. -J.;Tsai, C. -N.

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背景:半胱氨酰组织蛋白酶及其抑制剂半胱氨酸蛋白酶抑制剂(stens)的失调暗示着肿瘤发生的进展;方法:通过人Affymetrix U133A基因芯片、实时聚合酶链反应(PCR)和免疫组织化学数据揭示组织蛋白酶和stefins在IP和正常组织中的差异表达。结果:在组织蛋白酶和stefins家族中,组织蛋白酶S和stefin A的表达差异最大与正常组织相比,IF 组织中(分别下调和上调)。通过实时PCR验证其表达水平,结果显示与正常鼻窦粘膜相比,IP组织中组织蛋白酶S的表达水平显着下调,而stefin A的表达水平显着上调。免疫组织化学检测正常鼻窦黏膜间质区​​和上皮区巨噬细胞均可见组织蛋白酶S表达,而IP组织中未见明显组织蛋白酶S表达。相比之下,IF增殖鳞状细胞的几乎所有层中均存在stefin A的过表达,但仅在正常鼻窦粘膜的零星区域检测到stefin A的表达。结论:与正常鼻窦粘膜组织相比,IP组织中组织蛋白酶S的表达水平下调,而其内源性抑制剂stefin A的表达水平上调。鼻腔 IP 中 stefin A 和组织蛋白酶 S 反向表达的生物学意义需要进一步研究。
Background: Dysregulation of cysteinyl cathepsins and their inhibitors, cystatins (stens), 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 IF 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 IF, 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.