Hydrolytic enzyme activities, migratory activity, and in vivo growth and metastatic potential of recent tumor isolates.

19), and the high hydrolase levels may contribute to both decreased adhesiveness and abnormal migratory responses. These characteristics may, in addition, contribute to the malig nant behavior of tumor cells in vivo (16, 25). Following the work of Fidler (7) with the Bi 6 melanoma, several studies have shown that cultures of uncloned tumor cells contain phenotypically distinguishable subpopulations (6, 10, 17). We have recently described the establishment, from an uncloned population of mouse fibrosarcoma cells, of a subpopulation of cells by selection of the cells in medium containing 10% human serum in place of fetal calf serum (22). As compared to the uncloned fibrosarcoma cells, the human serum-adapted cells had lower levels of glycosidase and glu curonidase activity and elevated levels of esterase activity when measured using a substrate specific for chymotrypsin like enzymes. In addition, the human serum-adapted cells did not migrate as actively as did the uncloned cells in medium with fetal calf serum. When injected into syngeneic mice, the human serum-adapted cells were much less malignant than were the uncloned cells. While the uncloned cells produced tumors in 20 of 20 animals and spontaneously metastasized in 7 of these animals, the human serum-adapted cells produced tumors in only 6 of 30 animals with none demonstrating spon taneous metastases. The current study was done as part of our efforts to deter mine the relationship between various tumor cell properties and the ability of these cells to demonstrate malignant potential in vivo. In this study, we compared the in vitro properties and in vivo behavior of tumor cell populations isolated in culture from either primary or metastatic tumors from animals given injections of the uncloned fibrosarcoma cells or from animals given injections of the human serum-adapted cells.