Intraepithelial expression of perlecan, a basement membrane-type heparan sulfate proteoglycan reflects dysplastic changes of the oral mucosal epithelium
Intraepithelial expression of perlecan, a basement membrane-type heparan sulfate proteoglycan reflects dysplastic changes of the oral mucosal epithelium
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DOI：
10.1111/j.1600-0714.2004.00026.x
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发表时间：
2004-02-01
影响因子：
3.3
通讯作者：
Saku, T
中科院分区：
文献类型：
--
作者：
Ikarashi, T;Ida-Yonemochi, H;Saku, T
背景：基膜上一种主要的硫酸肝素蛋白聚糖（HSPG）在成釉细胞瘤或牙胚中的细胞间沉积可导致特征性的星状网状结构。虽然细胞间隙增大是口腔黏膜上皮发育不良的组织学特征之一，但perlecan在这些上皮病变中的表达方式尚不清楚。方法：采用免疫组织化学和原位杂交的方法，对82例由正常上皮和增生性上皮、上皮发育不良和鳞状细胞癌组成的活检标本进行perlecan核心蛋白和硫酸肝素（HS）链的检测。结果：在正常上皮和增殖性上皮中，沿基底细胞和下棘细胞的细胞边界均存在过核蛋白和HS链，基底细胞中也存在HS链。随着上皮发育不良严重程度的增加，核心蛋白大量且广泛地沉积在上皮间隙以及上皮细胞从基底层到表层的细胞质中。其基因表达在蛋白沉积物周围的细胞中得到证实。另一方面，HS链在轻度发育不良中增强，而在中度和重度发育不良中减弱。在鳞状细胞癌中，无论是核心蛋白还是HS链都很少在肿瘤细胞中发现，但在基质中却大量存在。结论：研究结果表明，perlecan定位于口腔上皮细胞间隙，在发育不良的上皮细胞中过表达并沉积于上皮间隙，导致细胞内聚性降低。
BACKGROUND: Intercellular deposition of perlecan, a major heparan sulfate proteoglycan (HSPG) of the basement membrane, is known to result in characteristic stellate reticulum-like structures in ameloblastomas or tooth germs. Although enlargement of the intercellular space is one of the histological characteristics of epithelial dysplasia of oral mucosa, the mode of expression of perlecan is poorly understood in these epithelial lesions.METHODS: Eighty-two biopsy specimens consisting of normal and hyperplastic epithelium, epithelial dysplasia, and squamous cell carcinomas were examined for both perlecan core protein and heparan sulfate (HS) chains by immunohistochemistry and in situ hybridization.RESULTS: In normal and hyperplastic epithelium, perlecan core protein and HS chains were localized in the cell border of parabasal cells and lower prickle cells, and HS chains were also found in basal cells. With an increase in the severity of epithelial dysplasia, the core protein was heavily and extensively deposited in the interepithelial space as well as in the cytoplasm of epithelial cells from the basal to the surface layers. Its gene expression was confirmed in the cells around the protein deposits. On the other hand, HS chains were enhanced in mild dysplasia, but decreased in moderate and severe dysplasias. In squamous cell carcinomas, either the core protein or HS chains were found scarcely in tumor cells but abundantly in the stromal space.CONCLUSIONS: The findings indicate that perlecan is localized in the intercellular space of the oral epithelia, and that it is over-expressed in dysplastic epithelial cells and is deposited in their interepithelial space, which results in the histology of reduction of cellular cohesion.