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Updated: Aug 9, 2026
A 3D Organotypic Melanoma Spheroid Skin Model
Published on: May 18, 2018
Regression by differentiation in the Sinclair swine model of cutaneous melanoma
J F Greene1, C D Morgan, A Rao
1Department of Pathology, Scott & White Clinic and Memorial Hospital, Texas A&M University Health Science Center, Temple 76508, USA.
Abstract:
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.
Insights
Spontaneous melanoma regression in Sinclair swine involves tumor cells differentiating into pigment-laden cells, not macrophages. This study identifies tumor cell differentiation as a key regression mechanism in this melanoma model.
Area of Science:
- Veterinary Pathology
- Dermatology
- Cancer Biology
Background:
- Spontaneous regression of melanoma in Sinclair miniature swine is characterized by replacement of tumors with pigmented cells.
- These pigmented cells have been traditionally identified as pigment-laden macrophages (PLMs).
Purpose of the Study:
- To investigate the origin of the pigment-laden cells observed during spontaneous melanoma regression in Sinclair miniature swine.
- To determine if these cells are monocyte-derived macrophages or terminally differentiated melanoma cells.
Main Methods:
- Transplantation of swine melanoma explants into severe combined immunodeficient (SCID) mice.
- Examination of harvested transplant sites using routine light and electron microscopy.
- Fluorescence microscopy of Hoeschst-stained paraffin sections to determine cell origin.
Main Results:
- Complete regression occurred in most transplanted sites, with replacement by PLM-like cells.
- Hoeschst staining confirmed the swine origin of these cells, ruling out mouse macrophages.
- Ultrastructural analysis revealed premelanosomes within the cells of a partially regressed lesion.
Conclusions:
- The residual pigmented cells in regressing Sinclair swine melanoma are terminally differentiated melanoma cells, not macrophages.
- Tumor cell differentiation is a significant mechanism driving spontaneous regression in this melanoma model.
