Lager D J, Callaghan E J, Worth S F, Raife T J, Lentz S R
Department of Pathology, University of Iowa College of Medicine, Iowa City, USA.
Am J Pathol. 1995 Apr;146(4):933-43.
Thrombomodulin is a cell surface glycoprotein that functions as an anticoagulant. Although initially identified on endothelial cells, thrombomodulin is also expressed by other vascular cells, by mesothelial cells, and by epidermal keratinocytes. To determine whether thrombomodulin is expressed by epithelial cells in locations other than skin, we conducted a survey of thrombomodulin protein and mRNA in human epithelium. Thrombomodulin protein was detected by immunohistochemistry in all samples containing stratified squamous epithelium, including oral mucosa, larynx, esophagus, uterine ectocervix, and vagina. In these tissues, thrombomodulin staining localized to the suprabasal layer, with minimal staining observed in the basal or superficial layers of epithelium. Thrombomodulin was not detected in cuboidal, simple columnar, or pseudostratified columnar epithelium and was detected variably in transitional epithelium. Thrombomodulin staining was also observed in 21 of 26 cases of invasive squamous cell carcinoma and in several examples of squamous carcinoma-in-situ and squamous metaplasia. Expression of thrombomodulin mRNA was confirmed by in situ hybridization in both normal and malignant squamous epithelium. Full-length, functionally active thrombomodulin was demonstrated in cultured squamous epithelial cells. These data demonstrate that thrombomodulin expression correlates with the squamous phenotype and suggest that hemostasis is regulated by compartmentalization of procoagulant and anti-coagulant epithelial proteins.
血栓调节蛋白是一种作为抗凝剂发挥作用的细胞表面糖蛋白。尽管最初在内皮细胞上被鉴定出来，但血栓调节蛋白也由其他血管细胞、间皮细胞和表皮角质形成细胞表达。为了确定血栓调节蛋白是否在皮肤以外的部位由上皮细胞表达，我们对人上皮组织中的血栓调节蛋白蛋白和mRNA进行了一项调查。通过免疫组织化学在所有含有复层鳞状上皮的样本中检测到血栓调节蛋白，包括口腔黏膜、喉、食管、子宫颈外口和阴道。在这些组织中，血栓调节蛋白染色定位于基底层以上，在上皮的基底层或表层观察到最小程度的染色。在立方上皮、单层柱状上皮或假复层柱状上皮中未检测到血栓调节蛋白，在移行上皮中检测结果不一。在26例浸润性鳞状细胞癌中的21例以及几个原位鳞状细胞癌和鳞状化生的例子中也观察到血栓调节蛋白染色。通过原位杂交在正常和恶性鳞状上皮中均证实了血栓调节蛋白mRNA的表达。在培养的鳞状上皮细胞中证实了全长、具有功能活性的血栓调节蛋白的存在。这些数据表明血栓调节蛋白的表达与鳞状表型相关，并提示止血是由促凝血和抗凝血上皮蛋白的分隔来调节的。
