Interstitial Fluid Pressure, Fraction of Necrotic Tumor Tissue, and Tumor Cell Density in Human Melanoma Xenografts

Abstract

Interstitial fluid pressure (IFP) has been shown to differ substantially between individual tumors, but the tumor properties governing the intertumor heterogeneity in IFP have not been identified conclusively. The purpose of the work reported here was to investigate whether the fraction of necrotic tissue and the density of tumor cells are major determinants of the intertumor heterogeneity in IFP. The study was based on the hypothesis that the resistance against fluid flow in the tumor interstitium is influenced significantly by these parameters. Xenografted tumors of four human melanoma lines (A-07, D-12, R-18, U-25) were included in the study. Tumors showing large variation in necrotic fraction but similar cell densities (D-12, U-25) were used to study the influence of necrosis on IFP, whereas tumors showing no or insignificant necrosis but large variation in cell density (A-07, R-18) were used to search for correlations between IFP and cell density. IFP was recorded using the wick-in-needle technique. Necrotic fraction and cell density were measured by stereological analysis of histological sections using an image processing system. Significant correlations between IFP and necrotic fraction were not found, implying that the IFP of tumors is not influenced significantly by the development of necrosis. The R-18 tumors, which had a high cell density, showed a significantly higher IFP than the A-07 tumors, which had a low cell density. Significant correlations between IFP and cell density were not found when individual tumors of the same line were considered. These two observations suggest that the IFP of tumors depends on the cell density, but the cell density is probably not a major determinant of the IFP.