Microvascular permeability of human melanoma xenografts to macromolecules:Relationships to tumor volumetric growth rate, tumor angiogenesis, and VEGF expression

The effective microvascular permeability of human melanoma xenografts to al bumin-Evans blue was measured and related to tumor volumetric growth rate, rate of tumor angiogenesis, and expression of vascular endothelial growth f actor (VEGF) in an attempt to identify mechanisms regulating the microvascu lar permeability of tumors to macromolecules. Three melanoma lines (A-07, R -18, and U-25) were included in the study. Effective microvascular permeabi lity was assessed by using the indicator diffusion method. Intradermal and intratumor angiogenesis assays were used to measure the rate of tumor angio genesis. VEGF expression was studied by ELISA, immunohistochemistry, Wester n blotting, and measurement of tumor-induced formation of ascitic fluid. Th e effective microvascular permeabilities of albumin-Evans blue were determi ned to be (1.5 +/- 0.2) x 10(-6) cm/s (A-07), (1.1 +/- 0.4) x 10(-6) cm/s ( R-18), and (0.9 +/- 0.3) x 10(-6) cm/s (U-25). These values are high compar ed with those measured for other tumor lines and are not significantly diff erent. Correlations between the effective microvascular permeability of alb umin-Evans blue and tumor volumetric growth rate, rate of tumor angiogenesi s, or VEGF expression were not found. The three last-mentioned parameters d iffered 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 showin g low VEGF expression. (C) 2001 Academic Press.