In vivo induction of tumor variants by phorbol 12-myristate 13-acetate

Malignant cells within solid tumors commonly exhibit phenotypic changes such as alterations in karyotype and acquisition of the ability to invade and to metastasize. We have used a fibrosarcoma, grown subcutaneously in C57BL/6 mice, to study the mechanisms underlying this phenotypic instability. Tumor-bearing animals were injected with phorbol myristate acetate (PMA) and then the tumors were transplanted to animals without further PMA treatment. These tumor cells were tum+, that is, unlike the parental tumors, they were able to grow in animals immunized against the parental tumors. This property was maintained for at least 6 tumor passages after the initial PMA injections. Thus, PMA appears to be able to induce an unstable tum+ phenotype in these cells at relatively high frequency.