Figure 2:

A schematic of EC reprogramming mediated by TEX. (A) Tumor cells produce and release exosomes. (B) TEX carry a variety of angiogenic proteins and in their lumen are enzymes, mRNA, miRNA and DNA. (C) TEX reach ECs carrying arrays or ‘bundles’ of several pro-angiogenic proteins. TEX reprogram ECs either by ligand/receptor signaling (1) and/or miRNA and mRNA transfers after fusion with the plasma membrane (2). ECs internalize TEX via endocytosis, phagocytosis, micropinocytosis or lipid raft-mediated internalization (3). All these pathways may result in an enhanced angiogenesis in vitro and in vivo. The molecular mechanisms engaged in EC reprogramming might include re-utilization of the delivered proteins and/or de-novo protein transcription from altered mRNA. The ECs reprogrammed by TEX express and secrete enhanced levels of angiogenic proteins. The proliferation, migration, and angiogenic activity of ECs are increased.