Differentiation of malignant to benign cells.

SUMMARY Rats bearing well-differentiated transplantable squamous cell carcinomas were given injections of thymidine-3 H, and the tumors were examined at intervals of time by radioautography with light and electron microscopes. Two hr after injection, labeled cells were almost exclusively in the undifferentiated areas of the tumor, and 96 hr after injection many cells of the well-differentiated pearls were labeled. These data suggest that the growth of the tumor was dependent upon proliferation of undifferentiated cells and that the growth of the pearls was dependent upon incorporation of undifferentiated cells into the pearl. Labeled cells that migrated into the pearls became well differentiated, as determined by electron microscopic radioautography, and when transplanted into compatible hosts did not form tumors. Thus it would appear that the progeny of malignant stem cells can differentiate into postmitotic benign cells incapable of forming a tumor.