Cytokeratins of Tumorigenic and Highly Malignant Respiratory Tract Epithelial Cells

Abstract

In malignant airway epithelial cells, structural abnormalities were evident from the cytokeratin organization. To determine whether the cytokeratins themselves were responsible, an in vitro model for bronchogenic carcinoma, consisting of three highly malignant lines and three less tumorigenic lines, was studied. Cytokeratins were evaluated by two-dimensional polyacrylamide gel electrophoresis (2D-PAGE). When typical constraints on tumors were relieved by in vitro culture, lines showed profiles resembling normal, primary cells. The CK5/CK14 combination, characteristic of basal epithelial layers, was represented by CK6A/CK14. CK17 was invariably present, while CK5, CK7, CK8, CK19, and CK42 content varied. CK19 appeared to substitute for the rarely observed CK18. While lacking the common CK8/CK18 combination of hyperproliferative cells, an invasive, metastasizing line had CK6A/CK7 or CK8 with CK19 suggesting derivation similar to adenocarcinomas. Bands of CK19 and actin migrated to higher pI in tumorigenic and malignant lines than in normal cells. Ubiquitinated acidic cytokeratins with a low isoelectric point (pI) and high molecular weight (MW) showed no consistent differences in lines that differed in growth potential. Type II made up 49–52% of total cytokeratins in nonmalignant lines, whereas highly malignant lines showed lower levels. Posttranslational modifications were identified but could not explain the shortfall of basic cytokeratins.