Enhanced growth of syngeneic, B16F10 melanoma in α2β1 integrin–deficient mice. (A) Tumor volume of B16F10 melanoma cells in α2-null mice (KO) and their wild-type (WT) littermates as a function of time. The data are presented as the mean plus or minus the standard error of the mean (SEM) with 18 animals of each genotype (P < .001, statistical analysis by ANOVA). (B) Photograph of tumors resected after 21 days (scale bar = 5 mm). (C) Representative photomicrograph of anti-CD31 antibody staining of tumor sections (scale bar = 50 μm; 20×/0.75 NA objective). (D) Total area occupied by CD31+ structures representing tumor vascular area as a percentage of total tumor area. Tumors from α2-null hosts show increased vascularity. Data are presented as the mean plus or minus SEM (9 tumors per genotype from 3 separate experiments; *P < .001). (E) The amplitude of blood flow within the tumor determined by power Doppler. There was a marked increase in blood flow to the tumor (as seen in yellow) in the α2-null mice in comparison to wild-type mice at 14 days after tumor injection. Total blood flow to the tumor was 7.68% (± 1.24%) in α2-null mice and 2.5% (± 0.43%) in the wild-type controls. A representative image from 3 separate experiments with 2 mice in each experiment is shown. (F) Representative low power images of hematoxylin and eosin–stained sections highlight tumor necrosis (necrosis outlined in black; scale bar = 100 μm; 10×/0.45 NA objective). (G) Tumor necrosis in wild-type and α2-null mice was morphologically quantitated. Necrotic area is presented as a percentage of the total tumor area from 5 low-power fields from 11 tumors per genotype. Data are presented as mean plus or minus SEM (*P = .002).