The degree of movement of embryonic cells, cells of established lines, and tumor cells will be studied in two in vitro culture systems in which cells contact only physiological substrates. In one system the penetration of (3H)-thymidine-labeled cells into aggregates of cells of the same type will be examined. In the second system, the migration of cells into collagen gels will be examined. A variety of normal, virally transformed and spontaneously transformed cell lines will be used, including BALB/c 3T3, SV40-BALB/c 3T3, MSV-BALB/c 3T3, NIL B, SV40-NIL B, chick heart fibroblasts (CHF), SV40-CHF, primary embryonic chick heart and RSV-CHF. The aim of these experiments is to determine if mobility in cellular aggregates or in collagen gels correlates with neoplastic transformation. The effect of dibutyryl cyclic AMP (dbcAMP) on mobility of cells in aggregates and in collagen gels will be determined. Also, the intracellular levels of cyclic AMP and cyclic GMP will be measured by radioimmunoassay to determine if cyclic nucleotide levels correlate with degree of mobility in all-cellular systems. Cell contact ultrastructure, occurrence of microvilli, and arrangement of microfilaments and microtubules will be examined by transmission and scanning electron microscopy in different cell lines, both with and without dbcAMP treatment. The aim is to determine what ultrastructural features of cells are correlated with enhanced mobility, and perhaps draw some conclusions concerning how cells move on physiological surfaces. The correlation between invasiveness and cellular mobility will be examined by testing the mobility of cells from invasive and non-invasive hamster and mouse tumors. Mobility will be examined as before, in aggregates and in collagen gels. Tumors will be re-implanted and mobility retested to determine if mobility also increases in multiple-passage tumors selected for invasiveness.