In order to characterize cell-cell and cell-substrate adhesion changes that are critical factors in the regulation of growth and development, we have employed two model systems: a) ethionine-transformed rat liver epithelial cells (line TRL 1215) for which controls at low and high passage level are available, and b) mouse epidermis-derived promotable cells of line JB6. By using immunofluorescence-labeled probes against major matrix proteins, we established that transformation in liver cells is accompanied by increased cell-substrate adhesion and cell spreading, thereby showing, in this cell system, that the capability of anchorage-independent growth is not related to loss of cell-substrate adhesion. Extension of this study includes investigations in the modulation of cell behavior by individual components of the basement membrane such as laminin, fibronectin, and collagen. Results of this investigation provide evidence of increased sensitivity to fibronectin by the transformed cells, but more strongly demonstrate the autonomy of the transformed cells relative to the controls with respect to growth and attachment. To define the role of gap junctional communication in tumor promotion, nonpromotable, promotable and transformed epidermis-derived cells of line JB6, untransformed and transformed liver cells (TRL 1215), and NIH 3T3 cells were subjected to the tumor promoter 12-0-tetradecanoylphorbol-13-acetate (TPA) and cell communication was measured by transfer of 3H-uridine. Our study suggests that TPA inhibits intercellular communication only among tumorigenic JB6 cells that over-grow surrounding cells; promotable and nonpromotable initiated cells are not distinguished by this protocol. Inhibition of uridine transfer as a short-term assay for tumor promoters thus gives a false negative in this cell line and results of the assay in other lines should be interpreted with caution.
