Oncotic and hydrostatic pressure differences control the movement of fluid
and large molecules across the microvascular wall of normal and tumor tissu
es. Recent studies have shown that the interstitial fluid pressure in tumor
s is elevated and is approximately equal to the microvascular pressure. Whe
reas 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 p
ressure in tumor interstitium should be close to that in plasma. To this en
d, we first developed a chronic wick method for the direct measurement of o
ncotic pressures in the interstitial fluid of tumors grown in mice. We foun
d interstitial oncotic pressures in four human tumor xenografts to be highe
r than in s.c. tissue and comparable to that in plasma [rhabdomyosarcoma (R
D), 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 re
sults support our hypothesis that the oncotic pressure difference across th
e tumor microvascular wall is low. The high oncotic pressure in tumors is c
onsistent with the elevated interstitial fluid pressure, and it contributes
to the suboptimal delivery of large therapeutic agents to neoplastic cells
.