Melanoma of Sinclair swine provides a unique probe for studying the initiation, growth, and regression of human melanoma. The majority of human melanomas arise from preexisting nevi, are apparently influenced by host hormonal and immune status, and can undergo spontaneous regression. Swine melanomas exhibit similar characteristics. They arise from preexisting nevi, show generally rapid growth soon after birth, and regress during and following puberty. Our laboratory has been attempting to correlate histopathologic changes in tumor status with specific physiologic triggers of melanoma growth and regression. The most significant changes in the hormonal status of Sinclair swine occur during suckling, weaning, puberty, and maturity--times at which the majority of tumor growth is initiated or ceases. These studies have required a synthesis of the disciplines of reproductive endocrinology, molecular endocrinology, developmental biology, and tumor biology and have led to a formal collaboration to determine whether: (1) perturbations in plasma endocrine profiles are correlated with changes in tumor dynamics; (2) hormonal influences on tumor dynamics are receptor mediated; and (3) growth and metastatic potential are genetically predetermined and/or directly influenced by estrogen using athymic mice. We suggest that an in-depth examination of melanoma cells in culture and hormonal factors controlling swine melanoma growth will provide new information on molecular mechanisms regulating neoplastic transformation and regression and will lead eventually to novel diagnostic and therapeutic approaches for human melanoma. (N)
