Microvesicles (MVs) are highly specialized messengers that deliver vital biological cargo, such as DNA, RNA and proteins. The main functions of MVs are cell-to-cell communication and new biomarkers of diseases, including cancer, that play a crucial role in both physiological and pathological processes. Through juxtacrine signalling, MVs can provoke a phenotypic response in recipient cells. However, the lack of MVs-specific fluorescent dyes and analytical technologies for MVs poses a barrier to clinical translation. Herein, multi-modal imaging of monocytic MVs (from immune system cells) released from control cells and those from a model of immune system attack of bacterial infection, i.e., lipopolysaccharide (LPS) stimulation, and their interactions with cancer cells have been studied.<br/><br/>This has incorporated the use of a combination of advanced confocal fluorescence microscopy, together with Raman and FTIR spectroscopies enabling the detection, visualization and characterization of the biomolecular differences that occur in cancer cells as a result of uptake of LPS-stimulated MVs compared with control MVs from THP-1 monocytes. More interestingly, permeability assays with monolayers of brain endothelial cells show that: (i) some monocytic MVs can pass through the blood-brain barrier without altering junctions in the integrated of cell layer; and (ii) the uptake of monocytic MVs changes the population of released endothelial MVs. In addition, the new fluorophores are able to label MVs selectively compared with artificial liposomes. Our techniques further provide a novel tool for the real-time observation of MV release by cells and their interactions with other cells. The selective fluorescent staining of MVs enables significant new insights into how extracellular communication between different cell types might affect <i>in vivo</i> biochemistry. Our work offers an unprecedented approach to study MV biology with selective metal fluorescent stains that may make major contributions to understanding disease pathologies, such as cancer and degenerative- and pathogen-induced brain damage, and changes in extracellular vesicle signalling in response to treatments with metal anti-cancer drugs.

Versatile roles of extracellular vesicles in cancer biology: New fluorophores as novel selective nucleic base stains for cellular microvesicles

2019 Fall National Meeting

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