Mullerian Inhibiting Substance (MIS), a product of the fetal testis, initiates regression of the Mullerian duct, the anlagen of the uterus, fallopian tubes and upper vagina. This fetal regressor may be used to produce a similar effect against tumors derived from cell lines which respond to MIS in utero. The goal of this particular study is to purify the MIS receptor and with this tool to localize the sites of action of MIS. Two approaches will be used. The first entails the use of purified labeled MIS to bind the MIS receptor. The second approach will be to use a blocking monoclonal antibody to develop an antiidiotypic antibody to MIS which can bind to MIS receptor. Once obtained, receptors can be localized both to the Mullerian duct itself and to other potential sites of action. Purification of MIS receptor will allow the study of the mechanism of Mullerian duct regression since it is not certain whether the receptor resides in the mesenchyme or in the epithelium. In addition, since MIS is known to suppress neoplasia, the MIS receptor may be able to serve as a """"""""tumor marker"""""""" to which MIS tagged with a chemotherapeutic or radiomimetic agent may be delivered. After developing appropriate skills in immunology, biochemistry, tissue culture, and histochemistry, these techniques will be used to study the neuroblastoma tumor during the third year of the study. An analysis will be made of: 1) the influence and interaction of the microenvironment through which the embryonic neural crest cells migrate with the neuroblastoma by coculturing notochord and somites with tumor on the chorioallantoic membrane; 2) the migratory pattern of neuroblastoma cells transplanted into different regions of the early quail embryo. The goal of the latter study will be to: 1) identify what biologic modifiers are present in the matrix through which neural crest cells develop and through which they migrate; and 2) determine how these factors modulate the growth and development of the neuroblastoma. With this information manipulation of these modifiers or their analogues may result in a significant impairment in the growth of this tumor.
