Microvesicles: mediators of extracellular communication during cancer progression

Abstract

Microvesicles are generated by the outward budding and fission of membrane vesicles from the cell surface. Recent studies suggest that microvesicle shedding is a highly regulated process that occurs in a spectrum of cell types and, more frequently, in tumor cells. Microvesicles have been widely detected in various biological fluids including peripheral blood, urine and ascitic fluids, and their function and composition depend on the cells from which they originate. By facilitating the horizontal transfer of bioactive molecules such as proteins, RNAs and microRNAs, they are now thought to have vital roles in tumor invasion and metastases, inflammation, coagulation, and stem-cell renewal and expansion. This Commentary summarizes recent literature on the properties and biogenesis of microvesicles and their potential role in cancer progression.

Fig. 1.

Microvesicle shedding. Microvesicles are formed by the outward budding of the plasma membrane, as shown. Not all plasma-membrane proteins are incorporated into shed vesicles, although the topology of membrane proteins remains intact. Membrane proteins such as oncogene and other growth-factor receptors, intergrin receptors and MHC class I molecules, soluble proteins such as proteases and cytokines, as well as nucleic acids, have been found in microvesicles. Microvesicles appear to be enriched in some lipids such as cholesterol, whereas phosphatidylserine is relocated to the outer membrane leaflet specifically at sites of microvesicle shedding.

Fig. 2.

Working model for the trafficking of cargo to sites of microvesicle shedding. Recent studies suggest that a variety of proteins, including MHC class I, β1 intergrin receptors and VAMP3 – which are trafficked via specialized early recycling endosomes – are selectively incorporated into microvesicles. It is unclear whether cargo sorting occurs in endosomes so that pre-packaged vesicles are trafficked to the cell surface, or whether sorting occurs at the plasma membrane. Proteins trafficked via other pathways (dashed line) could also be delivered to microvesicles.

Fig. 3.

Tumor-derived microvesicles influence many aspects of cancer progression. By their ability to harness select bioactive molecules and propagate the horizontal transfer of these cargoes, tumor-derived microvesicles can affect a variety of cellular events to have an enormous impact on tumor progression.