Research Project
3175291
We intend to investigate the immunochemistry, structure, and function of human melanoma-associated antigen p97, one of the best characterized and most tumor-specific of the human tumor-associated antigens so far identified by monoclonal antibodies. Our goal is to use p97 as a model so as to obtain insight into the nature of human tumor-associated antigens and to open the way to more effective diagnosis and therapy of human cancer. For the entire project period we have three specific aims: I. Immunochemistry. We intend: (1) to generate and characterize monoclonal antibodies to additional epitopes of native and denatured p97; (2) to synthesize peptides based on the amino acid sequence of p97 for use as immunogens; and (3) to obtain anti-idiopathic antibodies to mimic conformational epitopes of p97 for use as immunogens. II. Structure. Our structural studies of p97 will comprise: (1) amino acid sequencing; (2) investigation of post-translational modifications, particularly carbohydrate and phosphate; and (3) examination of its structure at the cell surface. III. Function. We shall investigate: (1) the putative role of p97 in iron uptake, particularly to determine whether p97 offers an alternative to the transferrin receptor as a means of iron uptake by melanoma cells and (2) the association of p97 with neoplasia, particularly whether the presence of p97 in large amounts in melanomas is a consequence (or cause) of neoplastic transformation or rapid growth. (AG)
