Five types of cancer have been shown to respond to their appropriate embryonic fields. This proposal focuses on the regulation of murine melanoma by the embryonic skin. The mechanism appears to be operative at the time of arrival of normally migrating melanoblasts into the skin. This pattern is suggested by a clear cut difference in tumor incidence following in utero transplantation into specific sites in embryonic skin. In parallel with these in vivo findings, conditioned media from the specific sites in embryonic skin inhibit the growth of melanoma cells in vitro; this can be measured by inhibition of colony size, decreased uptake of tritiated thymidine or other bioassays. In optimal conditions growth of melanoma cells ceases, and the cells have altered morphology and fail to grow again in fresh growth media. The crude activity is stable to boiling and lyophilization and has been localized to two peaks by gel filtration. Proceeding on the hypothesis that our assays with melanoma have detected a developmentally regulated process (i.e. site specific in the skin) we plan to define the tissue specificities of the peaks from gel filtration, select the appropriate peak, purify it and define its biochemical properties by high pressure liquid chromatography, and prepare monoclonal antibodies to it. Virally transformed embryonic cells are a potentially rich source of the activity, and when sufficient amounts are available it will be tested in tumor bearing mice. Antibodies would be used to localize the activity in the embryo.