A sub-strain of Sinclair miniature swine develops an aggressive form of melanoma very similar to the human counterpart. This aggressive melanoma has the unique attribute of spontaneously regressing after a complete metastatic phase. Within this clinically relevant animal model, scientists have a rare opportunity to study development, regression, and therapeutic compounds in a spontaneously occurring malignant cancer.

Sinclair miniature swine were derived from pigs originally developed at the Hormel Institute in Minnesota. The Sinclair swine melanoma was first observed in 1967 in one animal of the Sinclair miniature swine breeding herd. Experimental breeding herds of melanoma swine currently are maintained at the Sinclair Research Center, Columbia, Missouri.

Sinclair miniature swine display cutaneous melanoma lesions at birth or develop lesions shortly thereafter. Most, if not all, subsequently remain free of tumors. The tumor regression observed in Sinclair miniature swine appears to be associated with an increase in host leukocyte mediated activity. Examination of swine melanoma lesions during the latter stages of melanoma growth has revealed that large numbers of pigment-laden macrophages have invaded the lesions with an apparent decline in the number of cells. Furthermore, other studies have reported that the melanoma bearing swine exhibited enhanced leukocyte reactivity to 3 M KCl extracts of swine melanoma cells using an antigen stimulated active rosette assay. This in vitro leukocyte reactivity appeared to correlate with tumor volume as leukocyte activity was greater in swine with a lower rate of tumor growth and lower tumor volume. This Sinclair miniature swine developed an immune response to the melanoma.

The Sinclair miniature swine melanoma model has many features in common with its human counterpart: 1). Tumors develop spontaneously; 2). Swine possess a wide spectrum of benign melanocytic lesions capable of malignant transformation; 3). Melanomas in pigs histopathologically resemble human superficial spreading melanoma; 4). Metastatic disease is correlated with deeply invasive cutaneous tumors; 5). The pattern of metastatic spread is analogous to the distribution of metastases in human melanoma; 6). The histopathology of cutaneous regression is similar; 7). A tumor-related immune response occurs in the host; 8). A genetic component is readily apparent that is comparable to the genetic component of some melanomas in man.

Sinclair miniature swine melanoma provides a unique opportunity to investigate host-tumor-cell interactions in a clinically relevant system. The miniature swine melanoma model has many features in common with human malignant melanoma. Furthermore, substantial evidence exists that host immunological factors play a role in the development, growth, and regression of this neoplasm. The Sinclair miniature swine melanoma model also provides an excellent system in which to investigate the progressive cellular changes during the transition from normal, through pre-malignant, to malignant and to metastatic melanoma, as well as the cellular change occur during the spontaneous regression of melanoma lesions. Sinclair miniature swine melanomas have the variety of histopathologic form in vivo. We have found that when these lesions are adapted to grow in vitro, the primary cultures are also morphologically variable. This finding, together with the observation that several swine melanoma lesions can progress and regress simultaneously in a single pig, suggests that tumor heterogeneity may play a significant role in the natural history of swine melanoma.

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