Fig. 5.

A proposed model clarifying the paracrine effects of TD-sEVs on endothelial cells. The model illustrates how sEVs derived from ovarian tumor cells deal with endothelial cells through modulating multiple angiogenic-related signaling pathways. a In a physiological state, SOCS5 functions as a negative regulator of the JAK-STAT pathway, which in turn modulates downstream signalings in endothelial cells. b Transfer of miR-141 by TD-sEVs may up-regulate the JAK-STAT pathway and VEGFR-2 signaling in part by targeting SCOC5 in HUVECs. Additionally, the induced NF-κB activation triggered by TD-sEVs which may be mediated by the intracellular ROS production is critical events in endothelial cell angiogenesis. This model may be an explanation for the vascular response within the microenvironment of ovarian cancer