VASCULAR DENSITY IN HUMAN-MELANOMA XENOGRAFTS - RELATIONSHIP TO ANGIOGENESIS, PERFUSION AND NECROSIS

Studies of interrelationships between physiological parameters of tumo urs are sparse. The possibility that vascular density might be related to the rate of angiogenesis, the rate of perfusion and/or the develop ment of necrosis was examined in the work reported here. Xenografted t umours of four human melanoma cell lines (A-07, D-12, R-18 and U-25) g rown orthotopically in BALB/c nu/nu mice were included in the study. V ascular density and fraction of necrotic tissue were determined by ste reological 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 Rb-86 uptake method. A-07 showed a higher vascular density, a higher rate of angiogenesis and a higher r ate of perfusion than the other lines. D-12, R-18 and U-25, which diff ered significantly in the rate of angiogenesis, showed similar vascula r densities and similar perfusion rates. Consequently, vascular densit y is not a sensitive measure of the rate of angiogenesis in the melano ma 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 art eriovenous shunts, occurred more frequently in D-12 and U-25 than in A -07 and R-18. (C) 1998 Elsevier Science Ireland Ltd.