Cancer becomes wasteful: emerging roles of exosomes^† in cell-fate determination

Abstract

Extracellular vesicles (EVs), including exosomes, have been widely recognized for their role in intercellular communication of the immune response system. In the past few years, significance has been given to exosomes in the induction and modulation of cell-fate-inducing signalling pathways, such as the Hedgehog (Hh), Wnts, Notch, transforming growth factor (TGF-β), epidermal growth factor (EGF) and fibroblast growth factor (FGF) pathways, placing them in the wider context of development and also of cancer. These protein families induce signalling cascades responsible for tissue specification, homeostasis and maintenance. Exosomes contribute to cell-fate signal secretion, and vice versa exosome secretion can be induced by these proteins. Interestingly, exosomes can also transfer their mRNA to host cells or modulate the signalling pathways directly by the removal of downstream effector molecules from the cell. Surprisingly, much of what we know about the function of exosomes in cell determination is gathered from pathological transformed cancer cells and wound healing while data about their biogenesis and biology in normal developing and adult tissue lag behind. In this report, we will summarize some of the published literature and point to current advances and questions in this fast-developing topic. In a brief foray, we will also update and shortly discuss their potential in diagnosis and targeted cancer treatment.

• multivesicular body (MVB)
• extracellular vesicles
• exosomes
• cell-fate ligands
• secretion
• signalling pathways

Acknowledgements

The authors apologize to those colleagues whose work could not be cited owing to space constraints. They thank Kyra Campbell, Elena Casacuberta, Andreu Casali, Jordi Casanova and David Martín for critical comments and discussion on this article.

Conflict of interest and funding

F. W. was supported by pole-emploi, France, and N. B.-R. and X. F.-M. were supported by the Spanish MICINN (BFU2009-08748).