Circulating microvesicles (MVs) have been described as important players in cell-to-cell communication carrying biological information under normal or pathological condition. MVs released by cancer cells may incorporate diverse biomolecules (e.g. active lipids, proteins and RNA) which can be delivered and internalized by recipient cells, potentially altering gene expression of recipient cells and eventually impacting disease progression. Leukemia in vitro model systems were used to investigate MVs as vehicles of protein-coding messages. Several leukemic cells (K562, LAMA-87, TOM-1, REH and SHI-1), each carrying a specific chromosomal translocation, were analyzed. In the leukemic cells these chromosomal translocations are transcribed into oncogenic fusion transcripts and the transfer of these transcripts was monitored from leukemic cells to MVs for each of the cell lines. Microarray gene expression profiling was performed to compare transcriptomes of K562 derived MVs and parental K562 cells. The data show that oncogenic BCR-ABL1 transcripts and mRNAs related to basic functions of leukemic cells were included in MVs. Further analysis of MVs cargo revealed a remarkable enrichment of transcripts related to cell membrane activity, cell surface receptors and extracellular communication when compared to parental K562 cells. Finally, co-culturing of healthy mesenchymal stem cells (MSCs) with K562 derived MVs displayed the transfer of the oncogenic message, and confirmed the increase of target cell proliferation as a function of MVs dosage. Implications: This study provides novel insight into tumor-derived MVs as carriers of oncogenic protein coding messages that can potentially jeopardize cell-directed therapy, and spread to other compartments of the body.
- Received September 12, 2016.
- Revision received January 30, 2017.
- Accepted February 1, 2017.
- Copyright ©2017, American Association for Cancer Research.