MELANIN SYNTHESIS AND CONTROL OF MALIGNANT MELANOMA

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Malignant melanoma offers some particular attributes that provide opportunities for improved diagnosis and chemotherapy by a guided missile approach. This proposal is based upon the following observations; a) the synthesis of melanin and melanosomes, i.e., melanogenesis, occurs exclusively in melanocytes and is greatly elevated in the neoplastic counterpart, malignant melanocytes; b) melanosomes consist structurally of matrix protein anc tyrosinase, the latter of which categorizes the conversion of tyrosine to dopa and dopaquinone to form melanin; c) the structural protein becomes markedly aberrant in malignant melanoma; and b) the metabolic pathway from tyrosin to melanin is irreversible thus permittin incorporation of tyrosinase substrate into metabolically polymer melanin. To the melanosomal structural matrix proteins specifically of unique to the malignant melamocyte, we were able to establish monoclonal antibodies against melanosomes and thereby we have succeeded to establish the improved immunodiagnostic tools to detect early lesion of malignant melanoma and estimate the prognosis of malignant melanoma patients. Secondly, by chemically modifying the melanin precursors of tyrosinase substrate, we succeeded to localize synthetic compounds in melanoma cells and thereby destroy them. Thus, our project provided, by dissecting our specific specific biological properties of the malignant melanocyte, a unique research directed a) early laboratory diagnosis, and b) rational chemotherapy of malignant melanoma. Specifically, we were able to characterize the biological component of the melanocyte and to develop practical application of experimental result for better management of patient care.