Abstract 3844: Tumor endothelial cell lines and their use for the identification of new tumor vascular targets during dysbiosis

Abstract The overall use of antibiotics has increased by more than 30% in recent years according to the centers of disease control and prevention (CDC). Moreover, many cancer patients are prescribed antibiotics, as a prophylactic or to treat infection, a frequent complication during cancer progression and treatment. Yet, tumor endothelial cell lines are scarce at best and tumor endothelial cell lines derived under dysbiotic pressure non-existent. In order to address this we generated ‘normal’ or orthobiotic and dysbiotic tumor endothelial cell lines. After validating their endothelial cell origin on a genomic, proteomic and functional level, we found that tumor endothelial cells derived from dysbiotic mice (TEC-Dys) were more sensitive to hypofractionated radiation doses (i.e. 6 Gy) as compared to tumor endothelial cells derived from orthobiotic mice, TEC-Ortho. In order to identify relevant tumor vasculature drug targets during dysbiosis, we used tandem mass tag mass spectroscopy and focused on the extracellular proteins significantly overexpressed in TEC-Dys, as compared to TEC-Ortho. C-Met fulfilled these criteria and we validated this histologically by comparing tumors with or without dysbiosis. Moreover, c-Met inhibitors Foretinib, Crizotinib, and Cabozantinib were significantly more effective against TEC-Dys than TEC-Ortho. Foretinib inhibited tumor growth to a greater extend during dysbiosis as compared to orthobiotic conditions. Thus, we surmise that tumor response in dysbiotic patients may be greatly improved by targeting dysbiosis-induced pathways, such as c-Met, as compared to the targets suppressed due to dysbiosis. These matched tumor endothelial cell lines generated under orthobiotic and dysbiotic conditions can now be used in in vitro and in vivo cell-based models, and provide an improved and specialized platform for current and next-generation anti-cancer drug discovery and development. Citation Format: Samir V. Jenkins, Mohammad Alimohammadi, Kieng B. Vang, Robert J. Griffin, Ruud P. Dings. Tumor endothelial cell lines and their use for the identification of new tumor vascular targets during dysbiosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3844.