Intercellular communication sets the pace for transformed cells to survive and to thrive. Extracellular vesicles (EVs), such as exosomes, microvesicles and large oncosomes, are involved in this process shuttling reciprocal signals and other molecules between transformed and stromal cells, including fibroblasts, endothelial and immune cells. As a result, these cells are adapted or recruited to a constantly evolving cancer microenvironment. Moreover, EVs take part in the response to anticancer therapeutics not least by promoting drug resistance throughout the targeted tumor. Finally, circulating EVs can also transport important molecules to remote destinations in order to prime metastatic niches in an otherwise healthy tissue. Although the understanding of EV biology remains a major challenge in the field, their characteristics create new opportunities for advances in cancer diagnostics and therapeutics.
Schematic representation of the flow of information regulated by EVs
and large oncosomes (LOs) during metabolic reprogramming.
EVs from glycolytic cancer cells can contain information that is fed to malignant or non-transformed cells (of cancer or stromal origin) and cause metabolic changes. For instance, significant alterations can be induced in CAFs that in turn respond by the release of EVs containing sufficient material to sustain the cancer cell metabolism. This intercellular reprogramming evidences the dependency between the tumor and its adapted microenvironment, whereby EVs can be seen as outsourced ‘investments’ undertaken to deliver metabolites and other material that promote tumor growth.