After recalling the slow emergence of the cell theory, stating that cells are the fundamental units of structures and functions in all living organisms, the widespread observations of extracellular vesicles (EVs) will be somemore detailed. The current EV classification, and their main characteristics will be recalled, together with their promising assets for the theranostics of many human diseases, including cancers. However, many challenges remain to be solved before achieving this goal.

There is a missing step between the accumulated biological knowledge about EVs during two decades and the many recent preclinical searches for efficient EVs applications in oncology. The main reason is the current complete lack of knowledge about how EVs are completing the current cell theory centered on cells acting as powerful "biological factories" highly protected from their environment by their plasma membrane. In a great breakthrough, EVs are now known to mediate important cell's interconnections, which were completely ignored before, and which are resting on many mechanisms, which need to be urgently deciphered. In preclinal studies dealing with a few human patients compared to controls, the huge amount of different cells-derived EVs generates an inextricable complexity.

To evidence unknown EV-mediated mechanisms, a simple cell model would be much more convenient. The microorganism Dictyostelium discoideum (Dd) is ideal to achieve this goal as a wonderful eukaryotic in vitro and in vivo cell model. In 1998, we have discovered Dd EVs as mediating a new multidrug resistance mechanism, and then the normal and physiological Dd cells-release of different EVs during both the well-separated growth and starvation-induced differentiation. Moreover, Dd cells are devoted with many other assets, and axenic Dd cells are very well suited for conditioned-medium experiments to study the influence of specifically generated Dd EVs upon naive Dd cells, as will be shown in this presentation.