This project is the continuation of the studies aimed at defining and further characterizing the factors that control the activation, proliferation, and differentiation of normal primordial germ cells in the mouse and their transition into the stem cells of benign and malignant teratomas. In the previous granting period, we have established and defined the optimal conditions for isolation and in vitro culturing of germ cells and the production of tumors. We shall now continue studying the tumorigenesis in this system by using a new recombinant inbred strain with a high spontaneous tendency for germ cell activation in transplanted genital ridges and will define the role of the host-related factors in the control of tumor formation. Special attention will be paid to hormonal and immune factors and the control of malignancy of tumors. Using the monoclonal antibody techniques, we shall define the stages of ontogenesis of primordial germ cells in the mouse and define the changes that hallmark their transition into tumor cells or differentiated testicular gonocytes. The pregonadal stages of germ cell ontogenesis will be studied to define their phenotype characteristics, developmental, and tumorigenic potential. The ultimate goal of these studies is to better our understanding of germ cell tumorigenesis in the gonad and the normal ontogenesis of germ cells that preceeds tumor formation. Specifically, in the next year we will: (1) continue studies on the production of teratocarcinomas from genital ridges transplanted to the adult host; (2) concentrate on the activation of germ cells with lectins; (3) determine the nature of lectin binding to germ cells and their derivatives; (4) continue to produce and characterize monoclonal antibodies reactive with mouse germ cells and their malignant derivatives; and (5) continue to study the human germ cell tumors with antibodies produced to cell surface specific markers. (M)
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