Augmented angiogenesis in the α2β1 integrin–deficient animals is mediated by PLGF. (A) Tumor growth of LLC-PLGF or vector-only (control) transfectants in α2-null mice (KO) and their wild-type (WT) littermates as a function of time over 14 days. Tumors expressing PLGF grew significantly faster in α2-null mice than in wild-type mice. The data are presented as the mean plus or minus SEM with 5 animals of each genotype (P = .007, statistical analysis by ANOVA). (B) Immunohistochemical analysis with anti-CD31 staining of LLC-control and LLC-PLGF tumor sections in wild-type (WT) and α2-null (KO) animals showed an increased vascular area and increased size of the LLC-PLGF tumor vessels in α2-null mice (scale bar = 50 μm; 20×/0.75 NA objective). (C, D) In both wild-type and α2-null mice, LLC-PLGF–stimulated tumor vessels occupied a greater percentage of tumor area (***P = .002 for WT and **P < .001 for KO) and were larger (***P = .006 for WT and **P < .001 for KO) than LLC-stimulated vessels. Total area of CD31⁺ vessels as a percentage of total tumor area (*P = .003) and average vessel size (*P < .001) were increased in α2-deficient hosts bearing LLC-expressing PLGF tumors in comparison to wild-type hosts bearing LLC-expressing PLGF tumors. Data are presented as the mean plus or minus SEM (5 animals for each tumor/genotype combination). (E) Tumor growth of B16 melanoma-shPLGF or GFP-only (control) cells in wild-type (WT) and α2-null (KO) animals as a function of time over 14 days. The data are presented as the mean plus or minus SEM with 5 animals of each genotype (P = .91, statistical analysis by ANOVA). (F) In both wild-type and α2-null mice, B16 melanoma-shPLGF–stimulated tumor vessels occupied a similar percentage of tumor area in wild-type and α2-null mice. Data are presented as the mean plus or minus SEM (5 animals for each tumor/genotype combination; P = .521).