1. Inhibition of VEGFA or macrophage-specific ablation of Vegfa from TIE2hi/VEGFAhi TMEM macrophages reduces vascular permeability and tumor cell intravasation.
Inhibition of VEGFA or macrophage-specific ablation of Vegfa from TIE2hi/VEGFAhi TMEM macrophages reduces vascular permeability and tumor cell intravasation. A, immunofluorescence imaging of tumor sections after blocking VEGFA with anti-VEGFA blocking antibody (B ). Tumors are stained for vasculature (CD31; green), 155-kDa dextran–TMR (red) and DAPI (blue), ZO-1 (magenta), or VE-Cadherin (magenta) as indicated, demonstrating changes in vascular permeability by extravascular dextran and vascular junction staining. Scale bar, 50 μm. B, quantification of extravascular 155-kDa dextran–TMR from A (n = 10; **, P = ); (C) circulating tumor cells (*, P = ); (D) vascular ZO-1 from A (**, P = 0.005); and (E) vascular VE-Cadherin from A (*, P = ). F, immunofluorescence of tumor sections stained for vasculature (CD31; green), 155-kDa dextran–TMR (red) and DAPI (blue), ZO-1 (magenta), or VE-Cadherin (magenta) as indicated, demonstrating changes in vascular permeability after ablation of Vegfa by extravascular dextran and vascular junction staining. Scale bar, 50 μm. G, quantification of extravascular 155-kDa dextran–TMR from F and (Vegfafloxn = 5, Vegfaflox;Csf1r-Cre n = 3; **, P = ); (H) circulating tumor cells (*, P = ); (I) vascular ZO-1 from F (**, P = ); and (J) vascular VE-Cadherin from F (*, P = ).
Allison S. Harney et al. Cancer Discovery 2015;5:
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