Endogenous APC protects the endothelial barrier by inducing VE-cadherin expression. Lung histology was assessed in C56Bl/6 mice treated with 200 μg control MCO1716 antibody (A,B,G,H) or APC blocking antibodies MPC1609 (C,D,I,J) or MAPC1591 (E,F,K,L) in the presence (B,D,F,H,J,L) or absence (A,C,E,G,I,J) of B16F10 cancer cells. (A-F) hematoxylin–eosin staining section showing normal histology of lungs treated with antibody alone (A,C,E) and virtual normal histology of lungs containing B16F10 cancer cell () and treated with MCO1716 (B) and MAPC 1591 antibody (F). Treatment with cancer cells at 1 hour after inoculation and MPC1609 antibody caused accumulation of erythrocytes in the alveolar walls (*), indicating extravasation (D). Bar = 50 μm. (G-L) Immunohistochemical staining of VE-cadherin showing endothelial cell adherens junctions () in lungs treated with antibody alone (G,I,K). Adherens junctions in lungs at 1 hour after cancer cell inoculation and treatment with MCO1716 and MAPC 1591 antibody was reduced in comparison to lungs that did not receive cancer cells. Adherens junctional staining is completely lost after treatment with cancer cells and MPC1609 antibody (J). In this case the alveolar walls were swollen. Erythrocytes were also stained positive for VE-cadherin. Bar = 10 μm.