Extracellular vesicles: emerging mediators of intercellular communication and tumor angiogenesis

Rapidly expanding solid tumors demand large quantities of nutrients and oxygen. Growing tumors exploit pre-existing vessels and/or develop new vessels (vascularization) to obtain these nutrients. Vascularization is classified into two main processes, vasculogenesis and angiogenesis. Vasculogenesis is the formation of primitive blood vessels by endothelial progenitors, and angiogenesis encompasses the subsequent remodeling processes, including growth and migration of endothelial cells, sprouting, and stabilization of these sprouts by mural cells (1,2). Tumor cells utilize these processes to satisfy their needs and grow (tumor angiogenesis), especially under hypoxic conditions. One of the pro-angiogenic mechanisms exploited by hypoxic cancers is hypoxia-inducible transcriptional factor (HIF)-mediated signaling. Hypoxia leads to stabilization and nuclear translocation of HIF-1α, and subsequently increases transcription of pro-angiogenic genes, including vascular endothelial growth factor (VEGF) (3). Overexpression of HIF-1α has been reported in various solid tumors including brain, bladder, breast, colorectal, ovarian, pancreatic, and prostate cancers (4,5), and increased vascularity is a hallmark of poor prognosis.