Vascular density in human melanoma xenografts: relationship to angiogenesis, perfusion and necrosis

Studies of interrelationships between physiological parameters of tumours are sparse. The possibility that vascular density might be related to the rate of angiogenesis, the rate of perfusion and/or the development of necrosis was examined in the work reported here. Xenografted tumours of four human melanoma cell lines (A-07, D-12, R-18 and U-25) grown orthotopically in BALB/c nu/nu mice were included in the study. Vascular density and fraction of necrotic tissue were determined by stereological analysis of histological sections. The rate of angiogenesis was measured by using the intradermal angiogenesis assay. The rate of perfusion was studied by using the 86Rb uptake method. A-07 showed a higher vascular density, a higher rate of angiogenesis and a higher rate of perfusion than the other lines. D-12, R-18 and U-25, which differed significantly in the rate of angiogenesis, showed similar vascular densities and similar perfusion rates. Consequently, vascular density is not a sensitive measure of the rate of angiogenesis in the melanoma lines studied here, but might adequately reflect the perfusion rate. Significant necrotic regions developed in D-12 and U-25, but not in A-07 and R-18, presumably because large-diameter vessels, possibly arteriovenous shunts, occurred more frequently in D-12 and U-25 than in A-07 and R-18.