Microvesicles Circulating in Plasma of Rats Contain DNA: Are These Small Vesicles a Main Source of Cell-Free DNA in Plasma?

Several studies have shown the importance of communication between tumor cells and their environment through releasing of small membrane vesicles, which are often named micro-vesicles. Although, most of proliferating cells have been demonstrated to be capable of secreting such vesicles, this shedding is exacerbated in tumor cells. Recently, reports have indicated that micro-vesicles contain nucleic acids in addition to membrane antigens and cytosolic proteins. On the other hand, although the presence of high amounts of tumor DNA in plasma of cancer patients has been repeatedly confirmed, it is as yet unknown as to how cell-free nucleic acids circulate in the plasma. The goal of the present study was to determine whether or not such circulating DNA might be related to small vesicles released into the bloodstream. Our results showed that plasma of tumor-bearing rats had elevated levels of micro-vesicles compared to plasma from healthy animals. Moreover, real-time PCR analysis of DNA extracted from such micro-vesicles demonstrated the presence of k-ras sequences, indicating that circulating vesicles contain genomic DNA. Thus, these findings allow us to postulate that plasma-derived micro-vesicles could be the vehicle of cell-free DNA circulating in plasma.