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Tumor Biology |
Edwin L. Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114 [Y. B., R. K. J.], and Institute for Physiology, Physiological Chemistry and Animal Nutrition, Ludwig-Maximillians-University, Munich, Germany 80539 [M. Sto., M. Sta.]
Oncotic and hydrostatic pressure differences control the movement of fluid and large molecules across the microvascular wall of normal and tumor tissues. Recent studies have shown that the interstitial fluid pressure in tumors is elevated and is approximately equal to the microvascular pressure. Whereas oncotic pressure in blood plasma of various species is known, no data are available on the oncotic pressure in the interstitial space of tumors. We hypothesize that because of the leaky nature of tumor vessels, oncotic pressure in tumor interstitium should be close to that in plasma. To this end, we first developed a chronic wick method for the direct measurement of oncotic pressures in the interstitial fluid of tumors grown in mice. We found interstitial oncotic pressures in four human tumor xenografts to be higher than in s.c. tissue and comparable to that in plasma [rhabdomyosarcoma (RD), 24.2 ± 4.7; squamous cell carcinoma (FaDu), 19.9 ± 1.9; small cell lung carcinoma (54A), 21.1 ± 2.8; colon adenocarcinoma (LS174T), 16.7 ± 3.0 mm Hg; s.c. tissue, 8.2 ± 2.3; plasma, 20.0 ± 1.6 mm Hg]. These results support our hypothesis that the oncotic pressure difference across the tumor microvascular wall is low. The high oncotic pressure in tumors is consistent with the elevated interstitial fluid pressure, and it contributes to the suboptimal delivery of large therapeutic agents to neoplastic cells.
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