A Brief Contact with Early Embryonic Cells Induces the Differentiation of Embryonal Carcinoma Cells

An assay system was developed to detect a switch of mouse embryonal carcinoma (EC) cells to the pathway for normal cell differentiation after a brief contact with normal embryonic cells. The system consisted of (1) the mixed aggregation of AT805 EC cells with 8-cell stage mouse embryos, (2) the stationary culture of the mixed aggregates into blastocysts and (3) the cell culture of inner cell masses isolated from chimeric blastocysts containing EC cells at 2, 3 and 4 days after the initiaion of chimeric aggregation. The number of foci of EC cells which appeared in the cultures of inner cell masses was decreased with a length of contact of EC cells with normal embryos as the mixed aggregates. After 4 days' contact, only fibroblastic and epithelial cells appeared in most cultures of inner cell masses. Examination of isozyme markers of GPI revealed that such cell cultures consisting of nonmalignant cells contained cells of tumor origin. Thus, it was concluded that a brief exposure to the environment of normal embryos can regulate the tumor cells to differentiate into non-malignant cells. This conclusion was substantiated by comparing the pattern of protein spots of the tumor cells with that of non-malignant cells of the tumor origin by two dimensional gel electrophoresis.