CYTOKERATINS IN NORMAL LUNG AND LUNG CARCINOMAS .1. ADENOCARCINOMAS, SQUAMOUS-CELL CARCINOMAS AND CULTURED-CELL LINES

The various epithelial cells of the lower respiratory tract and the carcinomas derived from them differ markedly in their differentiation characteristics. Using immunofluorescence, microscopy and 2-dimensional gel electrophoresis of cytoskeletal proteins from microdissected tissues the role of cytokeratin polypeptides as markers of cell differentiation was studied in epithelia from various parts of the human and bovine lower respiratory tract. The protein patterns were compared with those found in the 2 commonest types of human lung carcinoma and in several cultured lung carcinoma cell lines. By immunofluorescene microscopy, broad spectrum antibodies to cytokeratins stain all epithelial cells of the respiratory tract, including basal, ciliated, goblet and alveolar cells as well as all tumor cells of adenocarcinomas and squamous cell carcinomas. Selective cytokeratin antibodies reveal cell type-related differences. Basal cells of the bronchial epithelium react with antibodies raised against a specific epidermal keratin polypeptide but not with antibodies derived from cytokeratins characteristic of simple epithelia. When examined by 2-dimensional gel electrophoresis, the alveolar cells of human lung show cytokeratin polypeptides typical of simple epithelia while the bronchial epithelium expresses, in addition, basic cytokeratins as well as acidic polypeptides. Bovine alveolar cells also differ from cells of the tracheal epithelium by the absence of a basic cytokeratin polypeptide. All adenocarcinomas of the lung reveal a simple-epithelium-type cytokeratin pattern. Squamous cell carcinomas of the lung contain an unusual complexity of cytokeratins. Several established cell lines derived from human lung carcinomas (SK-LU-1, Calu-1, SK-MES-1 and A-549) show a uniform pattern of cytokeratin polypeptides, similar to that found in adenocarcinomas. Vimentin filaments are produced in all the cell lines examined, except for SK-LU-1. All epithelial cells from the trachea and lung contain cytokeratins; epithelial cells from different parts of the respiratory tract express different cytokeratins; and the bronchial epithelium is characterized by the occurrence of basic and acidic polypeptides which are absent from alveoli. A marked, probably related difference in cytokeratin expression is also seen between squamous cell carcinomas and adenocarcinomas. The possible value of analyses of cytokeratin polypeptide patterns in lung carcinomas and metastases is discussed in relation to the diagnosis and histogenesis of lung neoplasms. Monoclonal antibodies specific for individual cytokeratin polypeptides may be used as selective diagnostic tools for the differentiation and classification of lung carcinomas.