Increasing metastatic potential is associated with increasing genetic instability of clones isolated from murine neoplasms.

Abstract

The metastatic stabilities of clones derived from the murine UV-2237 fibrosarcoma, with low or high metastatic potential were examined after 60-72 days of continuous growth in vitro and in vivo. Subclones of the high metastatic clone exhibited a 140-fold variation in the production of experimental pulmonary metastases after i.v. injection into syngeneic C3H- mice. Subclones from the low metastatic clone varied only slightly (8-fold). Using cloned cells from 3 mouse tumors with differing metastatic potential, the spontaneous mutation rates of cells with low or high metastatic capacities were determined with respect to the selective genetic markers, 6-thiopurine resistance or ouabain resistance or both. In all cases, cells with high metastatic potential had a 3-7-fold increase in the rate of mutation (per cell generation) at both genetic loci as compared with their low metastatic but tumorigenic cell controls. The evolution of tumors from the benign to the malignant state could be the consequence of acquired genetic instability in the neoplastic cells.