Franke W W, Moll R, Mueller H, Schmid E, Kuhn C, Krepler R, Artlieb U, Denk H
Proc Natl Acad Sci U S A. 1983 Jan;80(2):543-7. doi: 10.1073/pnas.80.2.543.
Epithelial cells contain desmosomes, special intercellular junctions providing sites of membrane attachment for intermediate-sized filaments of the cytokeratin type (tonofilaments). Such sites of anchorage of tonofilaments appear as dense plaques on the cytoplasmic side of the desmosomal membrane. We have isolated desmosome-enriched fractions from bovine snout epidermis and tongue mucosa and have characterized the major protein associated with the desmosomal plaque. This protein occurs in equimolar amounts of two polypeptides of Mr 250,000 (desmoplakin I) and Mr 215,000 (desmoplakin II) which are chemically and immunologically related. Antibodies raised against desmoplakins allow the identification and localization of this protein in epithelial cells grown in tissues or in vitro and show crossreaction in species as diverse as man, mouse, and chicken. Using immunolocalization at the light and electron microscope levels, we show that these antibodies bind specifically to desmosomal plaques. Antibodies to desmoplakins have been used successfully for detection of desmosomal proteins in a broad variety of epithelium-derived human tumors, including primary carcinomas and their metastases, irrespective of the morphology of the specific tumor. Nonepithelial tumors examined have been negative. We propose to use antibodies to desmoplakins and to cytokeratins in pathological diagnosis as two independent markers for the positive immunocytochemical identification and classification of epithelium derived tumors.
上皮细胞含有桥粒，桥粒是一种特殊的细胞间连接结构，为细胞角蛋白类型的中等大小细丝（张力细丝）提供膜附着位点。张力细丝的这些锚定位点在桥粒膜的细胞质侧表现为致密斑。我们从牛鼻表皮和舌黏膜中分离出富含桥粒的组分，并对与桥粒斑相关的主要蛋白质进行了表征。这种蛋白质由分子量为250,000的两种多肽（桥粒斑蛋白I）和分子量为215,000的两种多肽（桥粒斑蛋白II）等摩尔量组成，它们在化学和免疫方面具有相关性。针对桥粒斑蛋白产生的抗体能够在组织中生长或体外培养的上皮细胞中鉴定和定位这种蛋白质，并且在人、小鼠和鸡等多种物种中显示出交叉反应。通过在光学显微镜和电子显微镜水平上进行免疫定位，我们发现这些抗体特异性地结合桥粒斑。桥粒斑蛋白抗体已成功用于检测多种上皮来源的人类肿瘤中的桥粒蛋白，包括原发性癌及其转移灶，而不论特定肿瘤的形态如何。所检查的非上皮性肿瘤均为阴性。我们建议在病理诊断中使用桥粒斑蛋白抗体和细胞角蛋白抗体作为两种独立的标记物，用于上皮来源肿瘤的阳性免疫细胞化学鉴定和分类。
