American Association for Cancer Research
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Supplementary Video 2 from RALBP1/RLIP76 Depletion in Mice Suppresses Tumor Growth by Inhibiting Tumor Neovascularization

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posted on 2023-03-30, 21:11 authored by Seunghyung Lee, Jeremy G. T. Wurtzel, Sharad S. Singhal, Sanjay Awasthi, Lawrence E. Goldfinger

MOV file - 696K, 3D muCT reconstruction of the vasculature in a B16F10 tumor derived in a RLIP76-/- mouse



RalBP1/RLIP76 is a widely expressed multifunctional protein that binds the Ral and R-Ras small GTPases. In the mouse, RLIP76 is nonessential but its depletion or blockade promotes tumorigenesis and heightens the sensitivity of normal and tumor cells to radiation and cytotoxic drugs. However, its pathobiologic functions, which support tumorigenesis, are not well understood. Here, we show that RLIP76 is required for angiogenesis and for efficient neovascularization of primary solid tumors. Tumor growth from implanted melanoma or carcinoma cells was blunted in RLIP76−/− mice. An X-ray microcomputed tomography-based method to model tumor vascular structures revealed defects in both the extent and form of tumor angiogenesis in RLIP76−/− mice. Specifically, tumor vascular volumes were diminished and vessels were fewer in number, shorter, and narrower in RLIP76−/− mice than in wild-type mice. Moreover, we found that angiogenesis was blunted in mutant mice in the absence of tumor cells, with endothelial cells isolated from these animals exhibiting defects in migration, proliferation, and cord formation in vitro. Taken together, our results establish that RLIP76 is required for efficient endothelial cell function and angiogenesis in solid tumors. Cancer Res; 72(20); 5165–73. ©2012 AACR.