The long-term objective of the proposed research is to continue the formation of a model system for cancer research based on the culture of Wilms' tumor. Due to the inherent properties of this tumor type, this system will provide a superior model system to assign the genetic events that lead to tumorigenesis, tumor progression and tumor differentiation.
The specific aims center on continuing to improve the cell culture conditions for the growth of the blastemal elements from both Wilms' tumors and normal fetal kidneys, the growth of the anaplastic variant, and other commonly occurring elements of Wilms' tumors. The second goal will be to define the conditions under which the blastemal component from both Wilms' tumors and fetal kidneys undergoes the differentiation process in culture and in vivo. Monoclonal antibodies to the blastemal elements will be generated to help define the changes which occur when the blastemal element undergoes differentiation into mature tubule, glomerular, and stromal elements. Studies are also proposed to develop conditions by which the anaplastic variant of Wilms' tumor can be selected from classical Wilms' tumors composed primarily of a blastemal element. Lastly, studies will be initiated to define the production and genetic regulation of insulin-like growth factor II in the cultured elements from Wilms' tumors as well as the blastemal element of normal kidneys. The completion of these studies will characterize a model system for cancer research and also provide fundamental knowledge regarding the pathogenesis of Wilms's tumors.
