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Heterotransplantation Model of Human Malignant Melanoma¹

New England Medical Center Hospital and Tufts University School of Medicine, Boston, Massachusetts 02111

A heterotransplantation model of human melanoma has been established in immunosuppressed Wistar-Furth rats. Heterotransplantation is accomplished by inoculating live cultured melanoma cells subcutaneously in Wistar-Furth neonates immunosuppressed with antithymocyte serum. Two different tumor cell lines (BeRo and HaLe) have been transplanted, and the BeRo line has been maintained through serial transplantation for up to 12 generations. The transplanted BeRo tumor line produced pigment, and both lines exhibited an aneuploid karyotype with the banding characteristics of human chromosomes. Multiple pulmonary metastases have been noted in one animal bearing a s.c. (BeRo) tumor transplant.

Membrane immunofluorescence studies with autologous and allogeneic human sera revealed discrete sites of cross-reacting antigen(s) on cell membrane of the melanoma cells both prior to and after heterotransplantation. Appreciable augmentation in the antigenicity of cell membrane characterized by an increased number of sites of immune complexes or by a complete ring of fluorescence was observed with the animal-passaged cells, as opposed to fewer sites of immune complexes on the cultured cells. Sera from several tumor-bearing rats also revealed circulating antibody directed against antigen(s) on transplanted melanoma cells, and often demonstrated cross-reaction with cells derived from several other melanoma cell lines. Further studies are underway to determine the nature and specificity of the circulating antibody.

The heterotransplantation model provides a close approximation of an in vivo situation that can be conveniently used in cytokinetic, chemotherapeutic, or other relevant biological studies concerning human melanoma.

¹ This work was supported by American Cancer Society Grant T-550 and National Institutes of Health Cancer Research Center Grant CA-12924-01.

² To whom requests for reprints should be addressed, at Tufts-New England Medical Center Hospitals, 171 Harrison Avenue, Boston, Mass. 02111.

Received 7/24/73. Accepted 9/24/73.