Metastatic behavior of an adriamycin-resistant murine tumor

The metastatic behavior of a murine fibrosarcoma (UV-2237M-ADMR) resistant to Adriamycin (ADM) (doxorubicin) was investigated. Subclones isolated from the UV-2237M-ADMR line, which originated from a single colony, generally displayed a similar degree of resistance to ADM (eight out of nine clones did not differ from this UV-2237M-ADMR line). In contrast, they differed significantly in their capacity to form lung colonies after i.v. injection (six of nine clones differed significantly from the UV-2237M-ADMR line, p less than or equal to 0.005, Mann-Whitney U test). The UV-2237M-ADMR cell line maintained resistance to ADM even after 17 weeks of growth in syngeneic mice, although a gradual decrease in resistance was observed over this time. Spontaneous metastases from the UV-2237M-ADMR tumor commonly retained resistance to ADM. Of 18 cell lines, each established from an individual lung nodule, 16 showed plating efficiencies in the presence of ADM comparable to that of the primary UV-2237M-ADMR tumor. The remaining two lines had partially reverted to the sensitive state. The i.v. administration of ADM significantly reduced the lung tumor burden of mice with ADM-sensitive UV-2237M tumors but failed to affect the lung tumor burden of mice with UV-2237M-ADMR tumors. The UV-2237M-ADMR tumor line, exhibiting as it does both drug-resistant and metastatic behavior, provides a useful model system with which to investigate the metastatic process and the development of drug resistance.