The long-term goal of the proposed research is the formation of a human cancer model system based on the childhood cancer, Wilms' tumor. The initial goal of the proposed research is to continue the development of cell lines representative of the various components comprising this tumor, especially the malignant blastemal element. Related to this goal, is the continued development and maintenance of tumor heterotransplants grown in nude mice. Together, these systems provide a readily available source of tissues and cells for the study of Wilms' tumor cell biology, both for the applicant and the scientific community. Using serum-free cell culture techniques, it is also planned to establish the culture conditions for the maintenance of the renal blastemal element from the normal fetal kidney for use in comparative studies with its malignant counterpart. The second goal of this research is the continued production and characterization of monoclonal antibodies to the blastemal element of Wilms' tumor and normal kidney. This is performed using standard hybridoma cell fusion techniques and histochemical characterization. The production and characterization of these monoclonal antibodies provides the first comprehensive panel of reagents to characterize the developing fetal kidney and its neoplasms. Lastly, studies are proposed to continue to define the role of growth factors in Wilms' tumors. Specifically, studies are proposed to define the role of IGF-2, N-myc, c-myc and PDGF in the growth and differentiation of normal and Wilms' tumor tissues and cell lines. Completion of the studies proposed would provide a valuable model system for the study of human cancer.
