The distinct traits of extracellular vesicles generated by transformed cells

Abstract

Intercellular communication mediated by extracellular vesicles (EVs), membrane-enclosed packages released by cells, plays important roles in several physiological and pathological settings. Moreover, EVs have been shown to contain molecular signatures that reflect their cell of origin, raising the possibility that EV cargo could potentially be used to diagnose disease. However, for this to occur, a better understanding of the differences between EVs generated by normal and diseased cells is needed. We recently discovered that the content and function of one major class of EVs, microvesicles (MVs), changes upon the induction of oncogenic transformation. Specifically, we found that MVs derived from fibroblasts induced to express an oncogenic form of Dbl (onco-Dbl) are highly enriched in the activated form of the non-receptor tyrosine kinase, focal adhesion kinase (FAK). The FAK associated with these MVs can be transferred to normal recipient cells, where it stimulates signaling events that induce a transformed-like phenotype. We further showed that MVs from several breast cancer cell lines, but not their normal counterparts, similarly contained FAK. Thus, the enrichment of a specific cargo in MVs from transformed/cancer cells may help promote cancer progression, as well as potentially serve as an early and sensitive indicator of disease.