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Hydrolytic Enzyme Activities, Migratory Activity, and in Vivo Growth and Metastatic Potential of Recent Tumor Isolates¹

Department of Pathology, University of Connecticut Health Center, Farmington, Connecticut 06032

We isolated from an uncloned population of mouse fibrosarcoma cells a subpopulation of cells by repeated passage of the cells in medium with human serum in place of fetal calf serum. The human serum-adapted cells had an altered pattern of hydrolytic enzyme activities, migrated less actively than did the uncloned cells, and were much less malignant than were the parent cells. Both the uncloned cells and the human serum adapted cells were used to establish tumors in syngeneic mice. A number of isolates from primary tumors or metastatic tumors were obtained from these mice and grown in culture. The enzyme and migratory activities of the isolates were compared, and the degree of cancer was examined. It was found that, relative to their respective parent cells, the recent tumor isolates all showed increased chymotrypsin-like esterase activity, increased glycosidase activity, and increased ß-glucuronidase activity. Of the three, glycosidase activity was increased the most. Migratory activity of the isolates obtained from the uncloned parent cells was also increased. Relative to the primary tumor isolates derived from the uncloned parent fibrosarcoma cells, the metastatic isolates had higher levels of enzyme activities and greater migratory activity. Although all recent isolates had certain common features (i.e., tendency toward higher levels of enzyme activities), the basic pattern of characteristics of each isolate reflected the characteristics of its respective parent. The isolates derived from the human serumadapted cells, like the human serum-adapted cells, showed increased esterase activity but decreased glycosidase and glucuronidase activities and decreased migratory activity relative to the uncloned parent cells. Likewise, the degree of cancer of the isolates was still much lower than the degree of cancer of the uncloned parent cells or of the isolates derived from the uncloned parent cells. Thus, a single passage of the human serum-adapted cells through syngeneic mice did not result in a reversion of the phenotype to that of the uncloned cells.

¹ This study was supported in part by Grant AI-09651 from NIH and by a grant from the Connecticut Research Foundation.

² To whom requests for reprints should be addressed.

Received 12/14/78. Accepted 3/20/79.