Effects of targeting endothelial mTORC1 on metastatic tumor cells
Tumor metastasis, the main cause of death in cancer patients, requires outgrowth of tumor cells after their dissemination and residence in microscopic niches. Nutrient sufficiency is a determinant of such outgrowth. Fatty acids (FA) can be metabolized by cancer cells for their energetic and anabolic needs, thereby supporting metastatic progression. The vascular endothelium serves as a barrier to access of molecules into tissues, but it is unclear how fatty acid delivery to early metastatic tumors is regulated. Using a mouse model of metastatic outgrowth in the lung, we show that tumor endothelium actively promotes tumor growth by transferring FA into developing metastatic tumors. Tumor burden was significantly reduced upon endothelial-specific targeted deletion of Raptor, a unique component of the mTORC1 complex (RptorECKO). The goal of this study was to investigate how endothelial mTORC1 alters metastatic tumor cells. Overall design: To model metastatic outgrowth, tail vein injection of LLC-GFP-luciferase cells was performed in control (WT) mice or those with a endothelial-targeted Raptor knockout (Raptor ECKO). GFP+ tumor cells were collected by cell sorting and gene expression analysis was evaluated. Four biological replicates were evaluated, which were  generated from independent experiments.