This project is aimed at characterizing parameters important to the growth and differentiation of melanocytes and their significance to such critical properties of transformed melanocytes (termed malignant melanoma) as their ability to grow as primary tumors and to metastasize. Our studies have identified, isolated and characterized several distinct melanogenic enzymes that interact to regulate the quality and quantity of pigment produced within melanocytes. These proteins are encoded within a family of tyrosinase-related genes that are specifically expressed by mammalian melanocytes. Interestingly, although expression of these genes is specific to pigment producing tissues, they are independently regulated following stimulation of differentiation. We have shown that the phenotypic properties of the melanins produced by these catalytic regulatory controls can differ dramatically and the effects on the functional and photoprotective properties of these melanins are being actively studied. Our laboratory has also continued its interactive collaborations on the characterization of melanoma-specific antigens that are abnormally expressed on transformed melanocytes and which play a role in the host's immune responses to tumor growth. Monoclonal antibodies specific for one of those antigens, termed B700, have now been shown to be cross-reactive with human melanoma and have proven to be a highly specific probe for detecting malignant melanoma. The B700 antigen has been shown to be the major active antigen in a melanoma vaccine being developed that has proven to be efficacious in a model for spontaneous metastasis of murine melanoma.
