An important area in cancer research is metastasis where tumor cells invade adjacent tissues and produce secondary tumors in distant parts of their host. Recent experimental evidence suggests that these characteristics are determined, in part, by cell surface properties. In a murine model system utilizing variant B16 melanoma cell lines it was demonstrated that cell lines with higher metastatic potential (defined by the formation of more metastases per input i.v. or s.c. tumor cells) could be derived by a regimen of passing tumors from secondary target sites into tissue culture, then reimplanting i.v. and repeating the process several times. Each successive line selected for lung, brain or ovary colonization produced significantly more metastases than parent line in target tissues. We propose to use these melanoma cell lines grown in vivo as ascites tumors or in vitro in tissue culture to determine the cellular characteristics responsible for their metastatic properties. Chemical, enzymatic and ultrastructural techniques will be utilized to study cells grown in vitro and in animals. Cell adhesive interactions will be examined by quantitative cell aggregation and attachment of radiolabeled melanoma cells, endothelial extracellular matrix and normal host blood cells. Invasion of melanoma cells will be examined in target and nontarget tissue using small tissue pieces in culture. Surface degradative enzymes (proteases and glycosidases) will be determined by quantitative assays using synthetic substrates and metabolically labelled tissue extracellular matrix. Cell surface glycoproteins and antigens will be identified and characterized using affinity chromatography on immobilized-lectins or -antibodies (produced by hybridoma techniques). Shedding of cell surface components and plasma membrane vesicles will be studied and the components or vesicles used to build drug-encapsulated liposomes in order to direct chemotherapeutic drugs to specific organ sites where metastases are likely.