YAP orchestrates heterotypic endothelial cell communication via HGF/c-MET signaling in liver tumorigenesis

Disturbance of heterologous cell communication is associated with a structural reorganization of the vascular niche, a process called capillarization, which is already initiated in early stages of liver tumor development. In this study, the molecular characterization of endothelial cell (EC) subpopulations from healthy livers and yes-associated protein (Yap)-induced liver tumors revealed a dynamic crosstalk between liver sinusoidal endothelial cells (LSECs) and capillary endothelial cells (CECs). Initial paracrine stimuli from parenchymal cells include the Yap/Tead4 target gene osteopontin (Opn), which promotes CECs expansion through the induction of c-Met and sensitization towards LSEC-derived hepatocyte growth factor (Hgf). In addition, Yap/Tead4-induced C-C motif chemokine ligand 2 (Ccl2) recruits bone-marrow-derived macrophages (BMDMs) with an unpolarized phenotype (M0) to the perivascular space of expanding CECs. 6 samples in total: 3 samples capillary endothelial cells (CECs) and 3 samples liver sinusoidal endothelial cells (LSECs), both groups isolated from C57Bl/6N mice