Pancreatic cancer-derived exosomes: new role in paraneoplastic syndromes?

Recent studies show that cells can communicate through the exchange of bioactive molecules via microvesicles. These small vesicles include ectosomes (100–1,000 nm) and exosomes (30–100 nm), which are shed or secreted by almost all cell types (1). Endosome-derived microvesicles, known as exosomes, are secreted as part of multivesicular bodies into the extracellular space. Secreted microvesicles can be engulfed by tissues locally or carried in biological fluids to distant sites in the body (2). Intercellular communication can be initiated through interactions between circulating microvesicles and transmembrane proteins of target cells. Microvesicles fuse with target cell membranes, transferring cell surface molecules and receptors from donor to recipient cells. In addition, target cells engulf exosomes through endocytosis, resulting in the intracellular release of bioactive molecules, which include proteins, lipids, microRNAs, mRNAs, DNA, and metabolites (3-6). Tumor exosomes have been shown to be involved in various biological functions such as promoting angiogenesis and inducing apoptosis of activated cytotoxic T cells to create an immunosuppressive microenvironment that promotes cancer progression (7-9).