NON-SMALL-CELL LUNG-CARCINOMA CELLS INVADE HUMAN BRONCHIAL-MUCOSA IN-VITRO

To study invasion of lung cancer in vitro a novel three-dimensional co culture assay consisting of living human tissues has been developed. M ulticellular spheroids initiated from a new large-cell lung carcinoma cell line (GaL23), found to be invasive in immunodeficient mice, were confronted with precultured bronchial fragments derived from mucosal b iopsies obtained during routine fiberoptic bronchoscopy. The bronchial fragments consist of a stromal core with scattered fibroblasts covere d by a continuous surface epithelium resting on a basal lamina. During the first 2 wk of confrontation, a gradual retraction of the bronchia l epithelium with subsequent adhesion of the tumor cells to the underl ying basal lamina occurred. The following week, a limited invasion of tumor cells into the bronchial stroma was seen. To facilitate the entr ance of tumor cells through the mucosal surface, the surface epitheliu m was removed prior to coculture by ethylenediaminetetraacetic acid (E DTA) buffer treatment. Upon confrontation, GaL23 cells then rapidly at tached to and migrated on the exposed basal lamina and an increasing n umber of tumor cells was seen in the stroma during the first week of c ulture. This model offers opportunities for studying mechanisms of lun g cancer adhesion, migration, and invasion using human bronchial mucos a as the natural target tissue.