Abstract

Large Oncosomes: New Frontiers for Cell-to-Cell Communication in Cancer

Dolores Di Vizio, Professor, Cedars Sinai Medical Center

Extracellular vesicles (EVs) are important mediators of intercellular mechanisms as they can shuttle from one cell to another a reservoir of functional molecules (bioactive proteins, nucleic acids and lipids). EVs are highly heterogeneous and differ by size, composition and function. As a common characteristic, they all are surrounded by a lipid bilayer and can act in the proximity of the cell or at distance. Given the abundance of cancer-derived molecules that can be found in each particle, EVs are being recognized as appealing biomarkers of diagnosis and prognosis. Because these molecules are functional, EV profiling has also the potential to identify therapeutic targets in the personalized medicine effort. Our team recently reported that highly metastatic cells export large (1-10 µm diameter) bioactive EVs (large oncosomes) that originate from the shedding of bulky membrane protrusions from the plasma membrane. We have demonstrated that the abundance of large oncosomes in the circulation and in tissues correlates with advanced disease in mouse models and human subjects. We show that DNA and RNA-Sequencing can identify tumor specific alterations in large oncosomes circulating in mice and patient plasma. Large-scale profile analyses demonstrate that large oncosomes represent a novel population of EVs enriched in tumor-derived molecules. Large oncosomes are thus valuable candidates for new biomarker profiles to be developed using tissue- and blood-based assays in combination.