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Protein Content and Enzymatic Assays of Interstitial Fluid from Some Normal Tissues and Transplanted Mouse Tumors^*

(The Cancer Research Division of Radiumhemmet, Karolinska Institutet, Radiumhemmet, Stockholm, Sweden)

Microscale assays are reported on interstitial fluid samples taken from solid unicentric tumor transplants. Comparison was made of the protein content and enzymatic activity of normal mouse plasma and peritoneal fluid in the same strain of mice. The cell-free tumor fluid had a higher protein content, about 5 per cent, than the peritoneal fluid. The total "over-all" dipeptidase activity per volume was increased about 40–100 times; the arginase and glutathione reductase activities were likewise increased from 5 up to 20 times, and the catheptic activity at pH 4.5 showed on an average a three-to fourfold increase in activity over the corresponding normal plasma activities.

The observed increases in enzymatic activity cannot be due to a general protein retention in the tumor compartment. It is suggested that the local enzymatic increase in tumor fluids is brought about mainly by leakage of proteins from the tumor cells; this view is supported by other independent in vitro data. Some implications are mentioned with reference to the utilization of interstitial proteins for cell nutrition. The increased catheptic activity seems further to have a bearing on the extracellular proteolysis postulated to partake in the destructive activity of tumor cells.

The observations provide additional evidence that neoplastic cells are characterized by increased permeability also under in vivo conditions.

^* This investigation was supported by grants from the Jubilee Fund of King Gustaf V, the Swedish Cancer Society, and the Jane Coffin Childs Memorial Fund for Medical Research, all of which support is gratefully acknowledged.

Received 12/ 3/59.

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