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Practical Spontaneous Metastasis Model for in Vivo Therapeutic Studies Using a Human Melanoma¹

Developmental Therapeutics Program, Division of Cancer Treatment, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, Maryland 21702 [R. H. S., J. P., B. J. A., J. G. M., M. R. B.]; Southern Research Institute, Birmingham, Alabama 35255 [D. J. D., S. D. H., D. P. G.]; Institute for Cancer Research, Norwegian Radium Hospital, Montebello 3, Oslo, Norway [O. F.]

In vivo studies aimed at therapy of spontaneous human tumor metastases have been hampered by the lack of practical experimental models. The LOX amelanotic melanoma model described here represents a transplantation model which rapidly and reproducibly results in spontaneous pulmonary metastasis following s.c. inoculation into athymic mice. Pulmonary lesions can be detected using a simple bioassay procedure which is useful for estimation of metastatic cell killing. Using this model we demonstrate that systemic therapy with cyclophosphamide or dacarbazine can produce metastatic cell killing consistent with complete eradication of established pulmonary metastases. This model may also prove useful for future experimental therapeutic studies aimed at prevention of metastases by manipulating tumor staging interval and treatment schedule.

¹ Supported in part by National Cancer Institute Contracts NO1-CM-47581 and NO1-CM-67911.

² To whom requests for reprints should be addressed, at Laboratory of Drug Discovery Research and Development, Developmental Therapeutics Program, Division of Cancer Treatment, National Cancer Institute-Frederick Cancer Research and Development Center, Building 1052, Room 121, Frederick, MD 21702-1201.

Received 12/ 4/90. Accepted 3/26/91.

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