Nature and biosynthesis of structural matrix protein in melanosomes: melanosomal structural protein as differentiation antigen for neoplastic melanocytes

Abstract

Two major classes of protein, i.e., structural matrix and enzymic, exist in the melanosome. In normal melanocytes, synthesis of these two components is under a strict genetic control with regulatory steps associated with transcription and translation coded with appropriate pigment genes. In abnormal neoplastic melanocytes, they become markedly aberrant. The aberrant melanogenesis can be typically manifested by an abnormality in fine structure of the melanosome. The fine structural heterogeneity of the melanosome can often be diagnostic to certain forms of malignant melanoma and dysplastic melanocytic nevus. This study brings about the importance of the structural matrix protein for the expression of fine structural heterogeneity in the melanosome by developing the 2 monoclonal antibodies, MoAb HMSA-1 and HMSA-2. The 2 MoAbs recognized the cytoplasmic antigen on paraffin embedded sections, which under immunoelectron microscopy and cell fractionation studies, were found to be localization the melanosome and smooth ER, but not Golgi complex and coated vesicles as seen in the tyrosinase studies. It is indicated (a) that the sites of the synthesis for the melanosomal protein and tyrosinase are different, (b) that the melanosomal structural protein is accumulated in the dilated vacuole of smooth ER from which the stage I melanosome is synthesized, (c) that the synthesis of melanosomal protein becomes markedly aberrant and directly reflects the abnormal fine structure of the melanosome and (d) the heterogeneity in synthesis of melanosomal protein as expressed by MoAb HMSA-1 and HMSA-2 is a useful adjunct for immunohistopathological differentiation of malignant melanoma cells from benign nevoid cells and normal melanocytes.