Exosomal miRNAs as cancer biomarkers and therapeutic targets

Intercommunication between cancer cells and with their surrounding and distant environments is key to the survival, progression and metastasis of the tumour. Exosomes play a role in this communication process. MicroRNA (miRNA) expression is frequently dysregulated in tumour cells and can be reflected by distinct exosomal miRNA (ex-miRNA) profiles isolated from the bodily fluids of cancer patients. Here, the potential of ex-miRNA as a cancer biomarker and therapeutic target is critically analysed. Exosomes are a stable source of miRNA in bodily fluids but, despite a number of methods for exosome extraction and miRNA quantification, their suitability for diagnostics in a clinical setting is questionable. Furthermore, exosomally transferred miRNAs can alter the behaviour of recipient tumour and stromal cells to promote oncogenesis, highlighting a role in cell communication in cancer. However, our incomplete understanding of exosome biogenesis and miRNA loading mechanisms means that strategies to target exosomes or their transferred miRNAs are limited and not specific to tumour cells. Therefore, if ex-miRNA is to be employed in novel non-invasive diagnostic approaches and as a therapeutic target in cancer, two further advances are necessary: in methods to isolate and detect ex-miRNA, and a better understanding of their biogenesis and functions in tumour-cell communication.

Role of exosomes in tumour-related pathways

 Through the transfer of oncogenic signals, exosomes promote tumorigenesis through interaction with local and distant cells. The intra-tumour transfer of exosomes can facilitate growth and invasiveness, as well as confer chemoresistance. The exosome-mediated activation of fibroblasts facilitates the remodelling of the microenvironment and angiogenesis to enhance growth and invasion of cancer. The direct transfer of tumour-derived exosomes to vascular endothelial cells can promote angiogenesis. Tumour-derived exosomes can also modulate immune function to increase activity of tumour-promoting immune cells and suppress anti-tumour cells. The activation of these and other pathways in distant sites generates a pre-metastatic niche that facilitates metastasis.