Cellular localization of thrombomodulin in human epithelium and squamous malignancies.
Cellular localization of thrombomodulin in human epithelium and squamous malignancies.
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发表时间：
1995-04
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通讯作者：
Donna J. Lager;Edward J. Callaghan;Stephen F. Worth;T. Raife;Steven R. Lentzt
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作者：
Donna J. Lager;Edward J. Callaghan;Stephen F. Worth;T. Raife;Steven R. Lentzt
凝血调节蛋白是一种具有抗凝作用的细胞表面糖蛋白。虽然最初在内皮细胞上发现血栓调节蛋白，但其他血管细胞、间皮细胞和表皮角质形成细胞也表达血栓调节蛋白。为了确定凝血调节蛋白是否在皮肤以外的上皮细胞中表达，我们对人上皮中的凝血调节蛋白和mRNA进行了调查。免疫组化法检测含层状鳞状上皮的所有标本中的血栓调节蛋白，包括口腔黏膜、喉部、食道、子宫外宫颈和阴道。在这些组织中，血栓调节蛋白染色局限于基底上层，在上皮的基底或浅表层中观察到很少的染色。在立方上皮、单柱状上皮和假层状柱状上皮中未检测到血栓调节蛋白，而在移行上皮中检测到的血栓调节蛋白各不相同。在26例浸润性鳞状细胞癌中的21例以及原位鳞状癌和鳞状化生的几个例子中也观察到血栓调节蛋白染色。原位杂交证实了正常和恶性鳞状上皮中血栓调节蛋白mRNA的表达。在培养的鳞状上皮细胞中发现了全长、功能活跃的血栓调节蛋白。这些数据表明，血栓调节蛋白的表达与鳞状表型相关，并表明止血是由促凝和抗凝上皮蛋白的区隔化调节的。
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.