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Metastatic Behavior of an Adriamycin-resistant Murine Tumor¹

Cancer Metastasis and Treatment Laboratory, LBI-Basic Research Program, NCI-Frederick Cancer Research Facility, Frederick, Maryland 21701

The metastatic behavior of a murine fibrosarcoma (UV-2237M-ADM^R) resistant to Adriamycin (ADM) (doxorubicin) was investigated. Subclones isolated from the UV-2237M-ADM^R 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-ADM^R 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-ADM^R line, p 0.005, Mann-Whitney U test). The UV-2237M-ADM^R 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-ADM^R 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-ADM^R 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-ADM^R tumors.

The UV-2237M-ADM^R 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.

¹ Research sponsored by the National Cancer Institute, Department of Health and Human Services, under Contract N01-CO-23909 with Litton Bionetics, Inc. The contents of this publication do not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the United States Government.

² To whom requests for reprints should be addressed. Raffaella Giavazzi is on leave from Istituto di Richerche Farmacologiche "Mario Negri," Milan, Italy. Her present address is Department of Cell Biology, M. D. Anderson Hospital and Tumor Institute, the University of Texas System Cancer Center, P. O. Box HMB-173, Houston, Texas 77030.

Received 4/26/83. Accepted 8/ 2/83.