Transformed and neoplastic phenotype: reversibility during culture by cell density and cell shape

The ability of parental and transformed mouse C3H (10T 1/2) cells to grow when held at a graded series of cell shapes (flat to round) was studied using substrata of decreasing adhesivity. The parental cells showed a decrease in growth when they reached the most rounded configurations. In contrast, transformed cells proliferated at the same rate regardless of cell shape. In addition, when transformed cells were serially passaged at low density on highly adhesive plastic, which maintained cells in a flat configuration, a reversion from the transformed phenotype to a non-transformed phenotype occurred with the concomitant return of growth control by cell shape. However, when transformed cells were passaged at low density on a substratum which prevented cell spreading, the reversion to the parental phenotype did not occur and the cells escaped the growth control of cell shape and remained tumorigenic. Thus, in this cell system it appears that a change in cell configuration can dictate whether or not the transformed and neoplastic phenotype will be expressed.