**2.4 Large oncosomes**

Large oncosomes (LO) are atypically large (1–10 μm diameter) cancer-derived extracellular vesicles (EVs), originating from the shedding of membrane blebs and associated with advanced disease [45]. They contain proteins and nucleic acids [46]. Proteins such as caveolin-1 and metalloproteinases 2–9 (MMP2, 9) and GTPase ADPribosylation factor 6 (ARF6) are reported to be contained in LO [45]. LO contain miRNA, mRNA and DNA, which transmit signaling complexes between cell and tissue compartments. They can propagate oncogenic information, including transfer of signal transduction complexes, across tissue spaces. Compared to other EVs such as exosomes and MV, LO remains a poorly characterized EV type. LO exerts some functional effects varying on different cells from a direct proteolytic activity to the activation of pro-tumorigenic signals into different types of target cells including other tumor cells or cells of tumor microenvironment [47]. LO has been identified in highly migratory and invasive prostate cancer cells [48]. Recent studies have found that LO can contribute to tumor progression because they are able to degrade directly ECM in vitro [45]. Other researchers again have revealed that they have the ability to establish a tumor growth-supporting environment. This they believe is through the export of specific oncogenic cargo to other tumor or stromal cells [49]. Prostate cancer cell–derived oncosomes contain bioactive MMP9 and MMP2 and exhibit proteolytic activity on gelatin. This suggests that they could be a means to focally concentrate proteases that facilitate migration of tumor cells, thus promoting metastasis [50]. Considering their atypical size and their specific release from cancer cells, LO are promising source of both diagnostic and prognostic markers in cancers.
