This project is aimed at characterizing: (1) the host immune response to malignant melanoma, and the role it plays in the progression of tumor growth and metastatic spread; (2) tumor specific proteins produced by melanoma cells in vivo and in vitro, to determine the mechanism of their formation, to examine the impact of their expression on tumor growth, and to study the feasibility of utilizing their specificity for the immunoassay and immunotherapy of melanoma; (3) the role of cell surface proteases in the cascade of events leading to metastatic spread of tumors; (4) the control mechanisms involved in the regulation of pigment production in normal and in transformed melanocytes. The results indicate that various murine melanomas (of spontaneous, ultraviolet light induced, and chemically induced origin) share common cell surface antigens which are capable of eliciting tumor rejection; these antigens have a specificity restricted to melanoma cells. One melanoma tumor specific antigen has been purified to homogeneity and partially characterized; it is a glycoprotein of 65 kilodaltons, which has biochemical and immunological homology to serum albumin; it has been shown to be effective in immunizing mice against subsequent challenge with melanoma in transplantation assays and demonstrates the potential immunological significance of tumor specific antigen expression on the progress of tumor growth. We have found that alteration of surface urokinase activity significantly affects the metastatic potential of melanoma cells, suggesting that this protease plays an important role in the metastatic sequence. We have produced and utilized monoclonal antibodies specific for the melanocyte specific enzyme, tyrosinase, to examine cellular control mechanisms functional in the response of melanocytes to varying environmental stimuli which affect pigmentation, such as melanocyte stimulating hormone.
