The Cellular And Biological Impact Of Extracellular Vesicles In Pancreatic Cancer

Simple Summary The increased incidence and global failure of ongoing therapies project pancreatic cancer as the second deadliest cancer worldwide. While our knowledge of pancreatic cancer cells' abilities and specificities has drastically improved based on multi-scaled omics, one must consider that much more remains to be uncovered on the role and impact of stromal cells and the established network of communication with tumor cells. This review article discusses how tumor cells communicate with the various cells composing the stroma and its implication in tumor cells' abilities, PDA (pancreatic ductal adenocarcinoma) carcinogenesis and therapeutic response. We will focus on extracellular vesicles-mediated crosstalk and how this multifaceted dialogue impacts both cellular compartments and its subsequent impact on PDA biology. Deciphering the interactions between tumor and stromal cells is a growing field of research to improve pancreatic cancer-associated therapies and patients' care. Indeed, while accounting for 50 to 90% of the tumor mass, many pieces of evidence reported that beyond their structural role, the non-tumoral cells composing the intra-tumoral microenvironment influence tumor cells' proliferation, metabolism, cell death and resistance to therapies, among others. Simultaneously, tumor cells can influence non-tumoral neighboring or distant cells in order to shape a tumor-supportive and immunosuppressive environment as well as influencing the formation of metastatic niches. Among intercellular modes of communication, extracellular vesicles can simultaneously transfer the largest variety of signals and were recently reported as key effectors of cell-cell communication in pancreatic cancer, from its development to its evolution as well as its ability to resist available treatments. This review focuses on extracellular vesicles-mediated communication between different cellular components of pancreatic tumors, from the modulation of cellular activities and abilities to their biological and physiological relevance. Taking into consideration the intra-tumoral microenvironment and its extracellular-mediated crosstalk as main drivers of pancreatic cancer development should open up new therapeutic windows.