Heterogeneity of Extracellular Vesicles and Particles: Molecular Voxels in the Blood Borne Hologram of Organ Function, Disfunction and Cancer

Extracellular vesicles (EVs) and particles (EPs) serve as unique carriers of complex molecular information with increasingly recognized roles in health and disease. Individual EVs/EPs collectively contribute to the molecular fingerprint of their producing cell, reflecting its identity, state, function and phenotype. This property is of particular interest in cancer where enormous heterogeneity of cancer cells is compounded by the presence of altered stromal, vascular and immune cell populations, which is further complicated by systemic responses elicited by the disease in individual patients. These diverse and interacting cellular compartments are dynamically represented by myriads of EVs/EPs released into the circulating biofluids (blood) during cancer progression and treatment. Current approaches of liquid biopsy seek to follow specific elements of the EV/EP cargo that may have diagnostic utility (as biomarkers), such as cancer cell-derived mutant oncoproteins or nucleic acids. However, with emerging technologies enabling high-throughput EV/EP analysis at a single particle level, a more holistic approach may be on the horizon. Indeed, each EV/EP carries multidimensional information (molecular voxel) that could be integrated across thousands of particles into a larger and unbiased landscape (EV/EP hologram) reflecting the true cellular complexity of the disease, along with cellular interactions, systemic responses and effects of treatment. Thus, the longitudinal molecular mapping of EV/EP populations may add a new dimension to crucial aspects of cancer biology, personalized diagnostics, and therapy.

Automated summary

Extracellular vesicles and particles are unique carriers of molecular information that play increasingly recognized roles in various aspects of health and disease. In cancer, the complex cellular interactions and systemic responses can be reflected in the molecular composition of the EVs/EPs released into the bloodstream. Current liquid biopsy approaches focus on specific elements of EV/EP cargo as potential biomarkers, but emerging technologies enable a more holistic analysis at the single particle level. Longitudinal molecular mapping of EV/EP populations may provide a new dimension for understanding cancer biology, personalized diagnostics, and therapy.