Tumor-derived Wnt1 reduced and normalized subcutaneous tumor vascularization, whereas Dkk1 caused the opposite effect. (A) Tumor growth in Wnt1^−D compared with Wnt1^+D condition (left; n = 12/group; **, P < 0.01; ***, P < 0.001) and mouse survival (right; n = 12/group). (B) Tumor volume for Dkk1^−D compared with Dkk1^+D condition (left; n = 12/group; *, P < 0.05; **, P < 0.01; ***, P < 0.001) and mouse survival of Dkk1^+/−D tumors (right; n = 12/group). (C, top) IF staining on subcutaneous Wnt1 tumors for CD31/PECAM-1, α-SMA, and TOPRO-3. (bottom left) Vessel density of subcutaneous Wnt1 tumors +/−DOX (n = 5 tumors/group, 10 pictures/tumor; **, P < 0.01). (bottom right) Association of α-SMA⁺ cells to ECs in Wnt1^+/−D tumors (n = 5 tumors/group, 10 vessels/tumor; ***, P < 0.001). (D) Same staining and experimental settings as in C for subcutaneous Dkk1^+/−D tumors (*, P < 0.05). (C and D) Insets show vessels in higher magnification. (E) Perfusion with isolectin revealed that vessels from control^−D, Wnt1^−D, and Dkk1^−D tumors exhibited blood flow. Bars: (C and D) 400 µm; (E) 200 µm. Error bars indicate SEM.