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The Interstitial Fluid of Solid Tumors

Tumor-Host Relations Section, Laboratory of Biochemistry, National Cancer Institute, Bethesda, Md.

The interstitial fluid of a solid tumor, consisting of the liquid phase interposed between the newly formed vascular walls of the tumor and the plasma membrane of the neoplastic cells, has been sampled from a chamber enclosed into the neoplastic mass. The "tension" of the interstitial fluid of normal and neoplastic tissues was sufficient to produce a continuous outflow from the sampling device. In some tumors, but not in all of them, the pressure needed to stop this outflow was twice as large as that required for the normal subcutaneous tissue, and it was similar to that measured in the skin after venous obstruction.

The sampling technic has been described in detail. Each sample was compared with the blood serum flowing into and out of the neoplastic mass, with the interstitial fluid obtained by the same technic from the normal subcutaneous tissue, with the peritoneal fluid, and with the lymph of the thoracic duct of normal and tumor-bearing rats. The fluids were first tested for sterility and then analyzed for total protein, nonprotein N, urea, free amino acids, glucose, lactic acid, total sterols, lipid phosphorus, chloride, sodium, and potassium.

The main purpose was a better characterization of the milieu in which the neoplastic cells live. The results refer to small tumors (5–10 gm.) of Walker carcinoma 256, Fibrosarcoma 4956, Hepatoma 5123, Hepatoma 7974, and Novikoff hepatoma.

The interstitial fluid of the tumor was characterized by a very low content of free glucose and high levels of lactic acid. Data are reported on the passage of glucose from the blood into the interstitial fluid of tumors, and they suggest that this passage occurs by means of a transfer mechanism and not by simple diffusion. A "fermentative type" of interstitial fluid, peculiar to the tumor, was produced also in tissues without any sign of neoplasia being present.

The concentration of proteins was about 33 per cent lower in the interstitial fluid than in blood serum of tumors. This reduction was constant for each tumor, persisted during growth, and disappeared only when the sampling device was surrounded by necrotic tissue. The -globulins were reduced, but the albumin-globulin ratio of the interstitial fluid was equal to that of blood serum.

The free amino acid level was generally higher in the tumor fluid than in serum of blood entering or leaving the neoplastic mass, but the behavior was not uniform, and no conclusion could be drawn.

The concentration of cholesterol and lipid phosphorus in the interstitial fluid of tumors was about one-fourth of that of blood serum; however, the values in the tumor and in normal subcutaneous fluid were similar.

The gross composition of tumor fluid was maintained as constant as that of thoracic lymph, normal peritoneal fluid, or subcutaneous fluid despite the presence of necrotic foci and the known changes in metabolism of the neoplastic cell population.

Received 11/ 8/63.

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