Interstitial Fluid Pressure and Capillary Diameter Distribution in Human Melanoma Xenografts

Tumors have been shown to differ substantially in interstitial fluid pressure (IFP), but the biological properties of tumors governing the intertumor heterogeneity in IFP have not been identified conclusively. The purpose of the work reported here was to investigate whether the IFP of tumors is influenced significantly by the diameter distribution of the capillaries and hence by the geometric resistance of the capillary network to blood flow. Tumors of three human melanoma xenograft lines (D-12, R-18, U-25) showing similar capillary densities were included in the study. IFP was measured using the wick-in-needle technique. Capillary diameter distribution was determined by stereological analysis of histological sections. The lines differed significantly in tumor IFP (P < 0.05) and capillary diameter distribution (P < 0.05). Mean IFP was 6 mm Hg (D-12), 17 mm Hg (R-18), and 11 mm Hg (U-25). The mean of the mean capillary diameter was 13.1 μm (D-12), 10.9 μm (R-18), and 12.0 μm (U-25). The sequence of the lines from low to high IFP was the same as the sequence of the lines from large to small mean capillary diameter: D-12, U-25, R-18. Also, individual tumors of the same line differed substantially in IFP and in mean capillary diameter. IFP ranged from 2 to 15 mm Hg (D-12), from 2 to 36 mm Hg (R-18), and from 4 to 30 mm Hg (U-25). Mean capillary diameter ranged from 11.0 to 14.6 μm (D-12), from 9.5 to 11.7 μm (R-18), and from 10.4 to 13.0 μm (U-25). Inverse linear correlations between tumor IFP and mean capillary diameter were found for each of the melanoma lines [P < 0.05, R2 = 0.85 (D-12); P < 0.05, R2 = 0.86 (R-18); P < 0.01, R2 = 0.93 (U-25)]. Moreover, the IFP and mean capillary diameter of individual tumors varied with tumor size in all lines. IFP decreased during tumor growth whereas mean capillary diameter increased with increasing tumor volume (P < 0.001). Taken together, these data suggest that the diameter distribution and hence the geometric resistance of the capillary network exerts significant influence on the IFP of tumors.