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J. Li, A. K. Andri, M. Setiawan, L. Tong, R. W. Beuerman, J. S. Mehta, S. Ti, D. Tan; Expression of S100 Proteins in Corneal Intraepithlia Neoplasia. Invest. Ophthalmol. Vis. Sci. 2010;51(13):2397.
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S100 proteins are the largest family of Ca-binding proteins and are involved in a number of activities including tumor development and metastasis, inflammation and formation of epithelial barrier. This study compared the expression of S100 proteins among normal conjunctival and limbal cells and ocular surface squamous cell carcinoma (SCC).
S100 gene expression was determined by quantitative PCR (qPCR), protein distribution was determined by immunofluorescent staining analysis. SCC tissues were obtained from consented patients undergoing excision surgery.
Normal limbal and conjunctival epithelial cells expressed multiple S100 genes and the transcripts of S100A2, 6, 8, 9 10 and 11 appear to be more abundant than the others. SCC tissues showed thickening of the squamous epithelium with local disruption of the basement membrane and epithelial cell invasion in the stroma. The hyperplasic epithelial cells are positive of CK4 and CK14 staining while the invaded epithelial cells showed positive CK3 and CK14 staining. S100A4 appeared to be secreted at the surface of peripheral cornea, limbal and SCC epithelium, but absent at the surface of the central cornea. No difference was observed on the distribution of S100A6 between healthy corneal/limbal and SCC tissue. Staining of S100A8 and A9, which were limited to the surface of corneal and conjunctival epithelia, was found several layers beneath the SCC epithelium. The most striking difference was observed on the expression of S100A2 and S100A10. While positive staining of both proteins were only observed in the basal layer of the normal limbal epithelium, both stained positive across the full thickness of SCC epithelium as well as in the invaded cells. The first few passages of cultured SCC cell also showed higher S100A2 and S100A10 expression than normal conjunctival and limbal epithelial cells, however, the expression levels decreased with increasing passage.
Specific S100 proteins mark the differentiation and proliferation capacity of ocular surface epithelial cells and are associated with hyperplasic proliferation of SCC epithelial cells.
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