Moll R, Krepler R, Franke W W
Differentiation. 1983;23(3):256-69. doi: 10.1111/j.1432-0436.1982.tb01291.x.
Human epithelial cells contain, intermediate-sized filaments formed by polypeptides related to epidermal alpha-keratin ("cytokeratins") which are expressed in different combinations in different epithelia. Using cytoskeletal proteins from human biopsies and autopsies we have examined, by two-dimensional gel electrophoresis and immunoblotting experiments, the cytokeratin polypeptide patterns of diverse primary and metastatic carcinomas and have compared them with those of corresponding normal epithelial tissues and cultured cells. Five groups of carcinoma cytokeratin patterns can be discriminated. (1) Cytokeratins typical of simple epithelia (polypeptides Nos. 7, 8, 18, 19) are expressed, in various combinations, by many adenocarcinomas, for example those of gastrointestinal tract. (2) Cytokeratins typical of stratified epithelia (Nos. 1, 5, 6, 10, 11, 14-17) are found, in various combinations, in squamous cell carcinomas of skin and tongue. (3) Complex patterns showing polypeptides Nos. 7, 8, 18, 19, and one basic component (No. 5 or 6) are detected in certain carcinomas of the respiratory tract and the breast. (4) Complex patterns containing cytokeratins widespread in stratified epithelia (Nos. 4-6, 14-17) as well as components Nos. 8 and 19 occur in diverse squamous cell carcinomas derived from non-cornified stratified epithelia, with or without additional small amounts of cytokeratin No. 18. (5) Patterns of unusually high complexity can be found in some rare tumors as is shown for a cloacogenic carcinoma. No significant qualitative changes of expression of cytokeratins were found when primary tumors and metastases were compared. When compared with cytokeratin patterns of normal epithelia, carcinomas of the first type usually display a high degree of relatedness to the tissue of origin. Other carcinomas do not express some of the cytokeratins present in the tissue of their origin and, vice versa, certain components which are minor or apparently absent in normal tissue are major cytokeratins in the corresponding tumor. These differences may be explained by cell type selection during carcinogenesis, but changes of expression during tumor development cannot be categorically excluded. The possibility of cell type heterogeneity within a given tumor is also discussed. Similarly complex patterns of cytokeratin polypeptides have been noted in certain cultured human carcinoma cell lines (e.g., A-431, RPMI 2650, Detroit 562, A-549) and can also be observed in cell clones. The possible value of analyses of cytokeratin patterns, by gel electrophoresis or specific monoclonal antibodies, in distinguishing different carcinomas by non-morphologic criteria is discussed.
人类上皮细胞含有由与表皮α-角蛋白（“细胞角蛋白”）相关的多肽形成的中等大小的细丝，这些细胞角蛋白在不同上皮中以不同组合表达。我们使用来自人类活检和尸检的细胞骨架蛋白，通过二维凝胶电泳和免疫印迹实验，研究了多种原发性和转移性癌的细胞角蛋白多肽模式，并将它们与相应的正常上皮组织和培养细胞的模式进行了比较。可以区分出五组癌的细胞角蛋白模式。（1）许多腺癌，例如胃肠道腺癌，以各种组合表达简单上皮典型的细胞角蛋白（多肽编号7、8、18、19）。（2）在皮肤和舌的鳞状细胞癌中发现了分层上皮典型的细胞角蛋白（编号1、5、6、10、11、14 - 17），以各种组合存在。（3）在呼吸道和乳腺的某些癌中检测到显示多肽编号7、8、18、19以及一种碱性成分（编号5或6）的复杂模式。（4）在源自非角化分层上皮的各种鳞状细胞癌中出现含有在分层上皮中广泛存在的细胞角蛋白（编号4 - 6、14 - 17）以及编号8和19成分的复杂模式，有或没有额外少量的细胞角蛋白编号18。（5）在一些罕见肿瘤中可以发现异常高复杂性的模式，如泄殖腔源癌所示。比较原发性肿瘤和转移瘤时，未发现细胞角蛋白表达有明显的定性变化。与正常上皮的细胞角蛋白模式相比，第一类癌通常与起源组织有高度相关性。其他癌不表达其起源组织中存在的一些细胞角蛋白，反之，正常组织中少量或明显不存在的某些成分在相应肿瘤中是主要细胞角蛋白。这些差异可能由致癌过程中的细胞类型选择来解释，但不能完全排除肿瘤发展过程中表达的变化。还讨论了给定肿瘤内细胞类型异质性的可能性。在某些培养的人类癌细胞系（例如A - 431、RPMI 2650、底特律562、A - 549）中也注意到了类似复杂的细胞角蛋白多肽模式，并且在细胞克隆中也可以观察到。讨论了通过凝胶电泳或特异性单克隆抗体分析细胞角蛋白模式在通过非形态学标准区分不同癌方面的可能价值。
