Colony growth and clonogenic cell survival in human melanoma xenografts treated with chemotherapy

Abstract

A soft-agar diffusion-chamber technique was used to grow colonies from human melanoma xenografts. Plating efficiencies ranged from 0-042% to 75% and increased with serial passage of some tumours. Cells in colonies were similar to human melanoma cells in morphology, histochemistry and ultrastructure, and were shown by immunofluorescence to contain human antigens. Xenograft tumours could be regrown from the colonies when re-implanted into immune-deprived mice. Cell-survival curves were constructed from 5 xenograft lines treated with 4 cytotoxic drugs. All lines were resistant to adriamycin, but each line appeared to have an individual spectrum of sensitivity to the more effective drugs. The responses were compatible with the clinical pattern of response in melanoma, and in 2 cases the objective response of lung metastases to treatment with melphalan was consistent with the xenograft cell-survival data. Dose-response curves were exponential for treatment with methyl-CCNU and melphalan, but distinct plateaux were seen for 2 xenografts treated with doses of DTIC over 100 mg/kg. These were thought to be due to resistant subpopulations of clonogenic cells within the tumours.