Tumorigenicity of Human Malignant Melanocytes in Nude Mice in Relation to Their Differentiation in Vitro

Of 16 cell lines derived from 12 human melanomas obtained from 11 patients, all were established as permanent cell lines: 7 from primary tumors and 9 from metastatic tumors. Study of the early subcultures and established cell lines showed that melanocytes passed through a phase of dedifferentiation during which they took on a fibroblast-like appearance and were hypodiploid and nontumorigenic in nude (thymus-deficient) mice. Phenotypic modulation in vitro was shown to be dependent on the culture medium. The lines varied considerably in karyologic and phenotypic expression (as assessed by morphologic appearance and 5-S-cysteinyldopa production). Fibroblast-like, epithelioid, nonpigmented, achromic, and pigmented cells were obtained from the same tumor. Heterotransplantation into nude mice revealed wide variations in tumorigenicity: The latency of the tumors, their size, and infrequent metastases bore no relationship to the phenotypic modulation of the melanocytes as expressed in vitro. Melanogenesis is therefore not related to malignancy; they are two independent characteristics.