Loss of spontaneous metastasizing potential in mouse mammary tumors.

Among 25 C3H/He and C3Hf/He spontaneous mammary tumors that all had produced pulmonary metastases in the autochthonous mice, and also produced pulmonary metastases during subsequent sequential syngeneic intramammary passages, three were observed to stop producing metastases. The specific investigation of the observed changes in behavior is described. When the tumors were re-started in serial intramammary passage from early, cryopreserved transplant generations, the loss of metastasizing potential reoccurred in the same, or in nearly the same, transplant generations. In one tumor from which three transplant lines had been established, the metastasizing potential was lost in all transplant lines during closely related transplant generations. It seems that a spontaneous reduction of malignant behavior in mouse mammary tumors may be an occasional neoplastic characteristic, and that the observed losses of metastasizing potential may have been determined by a programmed genetic change.