Exosomes serve as tumour markers for personalized diagnostics owing to their important role in cancer metastasis

Abstract

Exosomes, membrane vesicles of 40-100 nm in diameter, are derived from endosomes in various cells. The bioactive molecules specifically packed into exosomes can be horizontally transferred into recipient cells changing their biological properties, by which tumour cells continuously modify their surrounding microenvironment and distant target cells favouring cancer metastasis. It has been suspected for a long time that exosomes participate in the whole process of tumour metastasis. Although there is much unknown and many controversies in the role of cancer exosome, the major contribution of tumour-associated exosomes to different steps of cancer metastasis are demonstrated in this review. Mainly because these exosomes are easily accessible and capable of representing their parental cells, exosomes draw much attention as a promising biomarker for tumour screening, diagnosis and prognosis. Currently, researchers have found numerous biomarkers in exosomes with great potential to be utilized in personalized medicine. In this article, we summarize the roles of biomarkers, which are validated by clinical samples. Even though many conundrums remain, such as exosome extraction, large multicentre validation of biomarkers and data interpretation, exosomes are certain to be used in clinical practice in the near future as the field rapidly expands.

Keywords: cancer biomarkers; extracellular vesicle; malignant neoplasms; metastasis; microenvironment; personalized diagnostics.

Fig. 1

The promotion of exosome to cancer metastasis. Tumour-associated exosomes influence other cells and modulate microenvironment, involving the key steps in cancer metastasis cascade. 1) In primary site, tumour cells secrete exosomes to induce EMT and degrade the matrix. The Wnt pathway in cancer cells is activated by exosomes during the migration. 2) As intravasation, endothelium is disturbed directly by tumour-secreted exosomes and indirectly by macrophages activated by exosomes derived from tumour cells. 3) Both circulating tumour cells (CTCs) and tumour-activated platelets secrete exosomes affecting the immune cells and CTCs. 4) Adhesive molecules on endothelial cells are upregulated by exosomes from the adherent tumour cell. 5) Disseminated tumour cells will proliferate forming a micrometastasis in appropriate niche, which is remoulded by exosomes from primary site.