Fig. 2. Enhanced angiogenesis at early stages of skin carcinogenesis in TSP-2-deficient mice. CD31 immunostains of blood vessels in untreated skin (A and B) and in early papillomas (C and D) of wild-type (A and C) and TSP-2-deficient (B and D) mice demonstrate strongly increased vascularization of papillomas, as compared with untreated skin, in both genotypes. Vascularization was much more pronounced in TSP-2-deficient papillomas (D) than in wild-type papillomas (C), with an increased number of enlarged blood vessels. Bar = 100 µm. (E) Computer-assisted quantitative image analysis of CD31-stained sections demonstrated that the average vascular area was significantly increased in TSP-2-deficient mice (filled bars) already at the stage of early papilloma formation and remained higher than in wild-type mice (open bars) throughout the progressive stages of skin carcinogenesis. Skin, untreated skin (n = 3); SP, small papillomas (≤3 mm; n = 7); LP, large papillomas (>5 mm; n = 6); SCC, squamous cell carcinomas (n = 2). Data are expressed as mean values ± SEM. **P <0.01. (F) Western blot analysis revealed comparable upregulation of VEGF expression in small (SP) and large (LP) papillomas and in SCC of both wild-type (lanes 1, 3, 5 and 7) and TSP-2-deficient (lanes 2, 4, 6 and 8) mice, as compared with untreated skin.