Microvascular Permeability of Human Melanoma Xenografts to Macromolecules: Relationships to Tumor Volumetric Growth Rate, Tumor Angiogenesis, and VEGF Expression

Abstract

The effective microvascular permeability of human melanoma xenografts to albumin–Evans blue was measured and related to tumor volumetric growth rate, rate of tumor angiogenesis, and expression of vascular endothelial growth factor (VEGF) in an attempt to identify mechanisms regulating the microvascular permeability of tumors to macromolecules. Three melanoma lines (A-07, R-18, and U-25) were included in the study. Effective microvascular permeability was assessed by using the indicator diffusion method. Intradermal and intratumor angiogenesis assays were used to measure the rate of tumor angiogenesis. VEGF expression was studied by ELISA, immunohistochemistry, Western blotting, and measurement of tumor-induced formation of ascitic fluid. The effective microvascular permeabilities of albumin–Evans blue were determined to be (1.5 ± 0.2) × 10−6 cm/s (A-07), (1.1 ± 0.4) × 10−6 cm/s (R-18), and (0.9 ± 0.3) × 10−6 cm/s (U-25). These values are high compared with those measured for other tumor lines and are not significantly different. Correlations between the effective microvascular permeability of albumin–Evans blue and tumor volumetric growth rate, rate of tumor angiogenesis, or VEGF expression were not found. The three last-mentioned parameters differed significantly among the melanoma lines and covered a broad range of values relative to those of other experimental tumors. Our study suggests that the effective microvascular permeability of macromolecules can be high even in slowly growing tumors, poorly angiogenic tumors, and tumors showing low VEGF expression.