Regression by differentiation in the Sinclair swine model of cutaneous melanoma

The spontaneous regression of melanoma in Sinclair miniature swine involves the replacement of tumours by pigmented cells, hitherto interpreted as pigment-laden macrophages (PLMs). We hypothesized that these residual cells are terminally differentiated melanoma cells, not monocyte-derived macrophages. Swine melanoma explants with no regression were transplanted into severe combined immunodeficient (SCID) mice. Harvested transplant sites were examined by routine light and electron microscopy techniques. Paraffin sections were also stained with Hoeschst dye and examined by fluorescence microscopy. All but one site had completely regressed and were replaced by PLM-like cells. Hoeschst staining indicated they were of swine, not mouse, origin. The ultrastructural features of the single, partially regressed lesion demonstrated many premelanosomes in these cells. We conclude that tumour differentiation is an important mechanism of regression in the Sinclair swine melanoma model.