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Shephard et al. Role of exosomes in prostate cancer

Figure 1: Overview of multiple roles of exosomes in prostate cancer. The previously described roles of prostate cancer exosomes are
varied. Many other potential roles demonstrated for exosomes, and/or EV, from other cancer types may also be applicable to prostate
cancer exosomes. Cancer exosomes can modulate the immune system. They can transmit tumor antigens to DC, or direct differentiation of
myeloid cells towards MDSC/anti-inflammatory (M2) macrophage phenotypes. Exosome-mediated delivery of RNAs can induce endothelial
cell proliferation, and exosome-associated proteins can induce endothelial tubule formation. Exosomal-TGFβ can induce differentiation
of stromal fibroblasts or MSC towards a pro-angiogenic and tumor supporting myofibroblast-like phenotype. Stromal cell-derived EV
can transfer chemoresistance to cancer cells and modulate both cancer cell metastasis and metabolism. Disease progression is further
enhanced by cancer exosomes, which have been shown to drive extracellular matrix remodeling and impair osteoclastic differentiation.
EV: extracellular vesicles; DC: dendritic cells; MDSC: myeloid-derived suppressor cell; MSC: mesenchymal stem cell; VEGF: vascular
endothelial growth factor; MMP: matrix metalloproteinase; FAK: focal adhesion kinase; IGFR: insulin-like growth factor receptor; Src: proto-
oncogene tyrosine-protein kinase Src; FGF2: fibroblast growth factor 2; uPA: urokinase-type plasminogen activator; HGF: hepatocyte
growth factor, PDGF: platelet-derived growth factor; TGFβ: transforming growth factor beta
activation of stromal cells to a disease-supporting roles for exosomes in prostate cancer, it is clear that
myofibroblast-like phenotype and may be capable exosomes are present and actively contribute to the
of modulating myeloid cells, thereby regulating disease process.
immune and inflammatory responses within the
tumor microenvironment. There is sufficient evidence It remains unclear why some men with prostate cancer
to suggest that exosomes are capable of regulating have slow growing, indolent, tumors whilst others
cancer cell metabolism and tumor metastasis, and develop aggressive late stage disease that is resistant
are capable of transferring drug resistance from one to treatment. There is therefore a growing demand for
cell to another. Such exosome-mediated effects, may improved assays capable of predicting those men who
impact tumor progression through direct or indirect are likely to develop aggressive disease. Due to the
mechanisms. Furthermore, it is not just cancer cell- elevated secretion of exosomes from neoplastic cells,
derived exosomes, but also exosomes from other cell their altered cargo, and their presence within numerous
types within the tumor microenvironment, which may biological fluids, there is substantial interest in the use
facilitate cancer progression. Whilst we may currently of exosomes as biomarkers for both diagnostic and
only be scratching the surface in terms of the possible prognostic monitoring of disease. Methodologies for
296 Journal of Cancer Metastasis and Treatment ¦ Volume 3 ¦ December 6, 2017