The role of microvesicles in malignancies.

Microvesicles are membrane-covered cell fragments whose size varies between 30 and 1,000 nm. They are generated by all cell types, constituvely and in response to activation signals. Their importance in intercellular communication has been only recently discovered. They seem to enhance the potential of information transfer between cells, displaying a large number of proteins and lipids as membrane constituents and as components of the inner vesicular content. The content reflects the phenotype of the donor cell and allows the identification of the microvesicular origine as well. Complex "packets" of molecules are transmitted to the target cells this way, modifying their cellular physiology. Additionally, epigenetic changes may be induced by transmitted DNA and RNAs, that have also been identified in these vesicles. The vesicles can act in close and far distances as well. Microvesicles have been implicated in several physiological and pathological processes. There is an increasing evidence, that they play a pivotal role in tumorigenesis. Vesicles shedding from tumor cells reflect the special potential of the tumor for survival and expansion, independently from cell-to-cell contact. Tumor derived vesicles are fully equipped to facilitate the escape of tumor cells from immune surveillance through their protein and RNA content, at the same time they are involved in the establishment of an optimal environment for newly formed and metastatic tumor cells, influencing angiogenesis and the reorganization of the extracellular matrix. As immune cells, endothels, platelets and stem cells also release microvesicles, a multilevel communication network draws up, allowing a complex interplay between the cells. The concentration of tumor derived vesicles increases in blood plasma and other body fluids with the progression of the disease; therefor they may serve as prognostic markers. The microvesicular approach can offer new perspectives: interfering with the formation, release and propagation of these vesicles, they can be considered as new targets in tumor therapy.