Figure 7.
Role of endothelial nitric oxide synthase in vascular endothelial protein tyrosine phosphatase (VE-PTP)–induced tumor vascular alterations. A) Human umbilical vein endothelial cell (HUVEC) nitric oxide production in vitro after treatment with control, AKB-9778, or NG-Monomethyl-L-arginine (L-NMMA). Nitric oxide production was determined by quantification of the fluorescent signal from DAF-2T. B) Representative images of DAF-2T fluorescence (green) in HUVECs after treatment with control (left panel), AKB-9778 (center panel), or AKB-9778 and L-NMMA (right panel) (scale bars = 20 μM). C) E0771 mammary carcinoma was implanted orthotopically into either wild-type (WT) C57Bl/6 mice or NOS3 -/- mice (KO). At tumor diameter of 3mm, mice were treated with either AKB-9778 or control vehicle (n = 5 per group). Data show tumor growth curves. eNOS = endothelial nitric oxide synthase. D) Vessel diameter in E0771 orthotopic mammary carcinomas treated with AKB-9778 or control vehicle in NOS3 -/- mice (P = .40 by two-sided t test; n = 5 per group). E) Vessel density in E0771 orthotopic mammary carcinomas treated with AKB-9778 or control vehicle in NOS3 -/- mice (P = .77 by two-sided t test; n = 5 per group). For all panels, error bars represent standard deviation.