Three-dimensional in vitro cocultivation of lung carcinoma cells with human bronchial organ culture as a model for bronchial carcinoma

We describe the development of a three-dimensional in vitro organ culture m odel for bronchial carcinoma using bronchial mucosa organ cultures and thre e different human non-small cell lung cancer cell lines. During precultivat ion, bronchial fragments obtained as biopsies during routine bronchoscopy h ad regenerated a complete epithelial covering with a well-preserved organot ypic architecture around a nucleus consisting of connective tissue. To crea te cocultures, different types of confrontation between tumor cells and org an cultures were applied. Histologic light microscopy and scanning electron microscopy were used in analysis. When tumor cells were confronted with co mpletely epithelialized organ cultures, they showed a low incidence of atta chment. When organ cultures were wounded before confrontation, tumor cells always attached to the wounded side and showed a progressive invasion into the stromal tissue. Measurements of the penetration depth of tumor cells in to the organ cultures after different incubation times permitted the quanti tative evaluation of invasion. Histologic studies revealed well-differentia ted normal epithelium in spite of long culture periods. Histologic features of the tumors were those of an invasive undifferentiated carcinoma and sho wed marked similarities to the situation in vivo. The coculture model permi ts internal controls because it contains both normal human epithelium and h uman tumor cells in the same organotypic culture. Therefore it offers oppor tunities for various in vitro investigations on therapeutic and diagnostic modalities of lung cancer, as indicated in this paper by an example of phot odynamic procedures with 5-aminolevulinic acid.