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Figure 5 | BMC Cancer

Figure 5

From: Combination of Dll4/Notch and Ephrin-B2/EphB4 targeted therapy is highly effective in disrupting tumor angiogenesis

Figure 5

Hepatic vascular lesions observed in endothelial-specific Dll4 knock-out mice are prevented by sEphB4-Alb administration. Representative pictures of hematoxylin and eosin staining of liver sections from induced, tamoxifen-treated (A and B) and non-induced, PBS-treated (C and D) Dll4 lox/lox Cre+ mice, and from induced, tamoxifen-treated Dll4 lox/lox Cre+ mice administered with PBS vehicle (E) or sEphB4-Alb (F) for 12 weeks to assess the effect of Ephrin-B2/EphB4 blockade combined with total inhibition of Dll4/Notch endothelial signaling. A, Ten weeks after the induction of endothelium-specific Dll4 loss-of-function, all studied 14-week-old Dll4 lox/lox Cre+ presented excessive sub-capsular vascular proliferation. The image shows vessels (arrows), some of which extremely dilated, occupying sub-capsular regions throughout the liver. B, Higher magnification of sub-capsular blood vessels (inset in A); C, Age-matched non-induced Dll4 lox/lox Cre+ presented normal liver histology. D, Higher magnification of the inset in C showing a single hepatic vessel that cannot be considered sub-capsular. E and F, Excessive vascular proliferation forming an hemangioma-like sub-capsular structure in a tamoxifen-induced Dll4 lox/lox Cre+ mouse injected with PBS and normal hepatic structure in a sEphB4-treated tamoxifen-induced Dll4 lox/lox Cre+ mouse, respectively. V, blood vessel; nEC, endothelial cell nucleus, RBC, red blood cells; H, hepatocytes.

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