Exosome in tumour microenvironment: overview of the crosstalk between normal and cancer cells

Abstract

Cancer development is a multistep process in which exosomes play important roles. Exosomes are small vesicles formed in vesicular bodies in the endosomal network. The major role of exosomes seems to be the transport of bioactive molecules between cells. Depending on the cell of origin, exosomes are implicated in the regulation of several cellular events, with phenotypic consequences in recipient cells. Cancer derived exosomes (CCEs) are important players in the formation of the tumour microenvironment by (i) enabling the escape of tumour cells to immunological system and help initiating the inflammatory response; (ii) acting in the differentiation of fibroblasts and mesenchymal cells into myofibroblasts; (iii) triggering the angiogenic process; and (iv) enhancing the metastatic evolution of the tumour by promoting epithelial to mesenchymal transformation of tumour cells and by preparing the tumour niche in the new anatomical location. Since the finding that exosomes content resembles that of the cell of origin, they may be regarded as suitable biomarkers for cancer diagnosis, allowing for diagnosis and prognosis via a minimal invasive procedure. Exosome involvement in cancer may open new avenues regarding therapeutics, such as vectors for targeted drug delivery.

Figure 1

Tumour microenvironment processes mediated by cancer cell derived exosomes (CCEs): (i) intratumour heterogeneity resulting from phenotype modification of normal cells after internalization of CCEs; (ii) inhibition of the immune response against tumour cells by inhibiting the proliferative response of lymphocytes; (iii) activation of the differentiation of fibroblasts into cancer associated fibroblasts; (iv) stimulation of the angiogenic process; and (v) epithelial to mesenchymal transition (EMT) and preparation of a premetastatic niche at the distant location.

Figure 2

Major groups of exosomes based therapies, which include the removal of cancer derived exosomes, containing bioactive molecules, from the blood (or other body fluids) of cancer patients through a haemodialysis-like process; activation of the immune system against cancer cells by the use of vaccines of exosomes containing proteins with higher expression in tumour cell membranes; and use of exosomes containing microRNA (miRNA), small interference RNA (siRNA), and/or anticancer drugs for targeting delivery to cancer cells.