Experimental approaches to problems of invasion and metastasis

The highly metastasizing ASML cells and the non-metastasizing AS cells, arisen as spontaneous tumors of the rat, were confronted with rat lung tissue in vitro. Small cubes of the lung were allowed to heal their cut edges, then tumor cells were added. Both tumor cell types adapted their shape to the environment, penetrated the superficial layer of lung cells, either of epithelial or of fibroblastoid character and settled on the basal lamina, which, however, was not pierced. In a second set of experiments the tumor cells were inoculated intravenously into the living animal. The lung loaded with tumor cells was excised and cut into cubes which were then incubated in vitro. Here also both tumor cell types exhibited an invasive behavior but the basal lamina of the vessels in which the tumor cells have been arrested was not penetrated. These data indicate that tumor cell behavior is strongly dependent on the environment and the complete invasion or extravasation must be considered as an inducible process.