Formation and role of exosomes in cancer

Abstract

Exosomes offer new insight into cancer biology with both diagnostic and therapeutic implications. Because of their cell-to-cell communication, exosomes influence tumor progression, metastasis, and therapeutic efficacy. They can be isolated from blood and other bodily fluids to reveal disease processes occurring within the body, including cancerous growth. In addition to being a reservoir of cancer biomarkers, they can be re-engineered to reinstate tumor immunity. Tumor exosomes interact with various cells of the microenvironment to confer tumor-advantageous changes that are responsible for stromal activation, induction of the angiogenic switch, increased vascular permeability, and immune escape. Exosomes also contribute to metastasis by aiding in the epithelial-to-mesenchymal transition and formation of the pre-metastatic niche. Furthermore, exosomes protect tumor cells from the cytotoxic effects of chemotherapy drugs and transfer chemoresistance properties to nearby cells. Thus, exosomes are essential to many lethal elements of cancer and it is important to understand their biogenesis and role in cancer.

Fig. 1

Exosomes. a TEM of plectin-positive pancreatic ductal adenocarcinoma (PDAC) cells with enhanced exosome production. Plectin is necessary for exosome production in PDAC and is aberrantly expressed on the cell surface through an exosome-mediated process (see [39] for details about PDAC exosomes). b Nanosight analysis of exosomes isolated from mouse serum using ExoQuick-TC isolation reagent shows the exosome size/concentration, a sample video frame of the exosomes, as well as the exosome size/relative intensity in both a scatter and 3D plot (unpublished image). c Exosomes can be differentiated from other secreted vesicles by their size (nm), density in sucrose (g/mL), and sedimentation speed (×g) (numbers from [18])

Fig. 2

Exosome Biogenesis. The plasma membrane buds inward, forming a membrane-bound vacuole. This endosome goes through several changes as it matures from an early endosome to a late endosome. Most notably, the endosomal membrane buds inward and pinches off to make membrane-bound vesicles inside the endosome and the endosome is now titled a multivesicular endosome (MVE). The MVE may travel to the lysosome and degrade its contents or it may travel to and fuse with the plasma membrane, releasing its contents, which, once existing outside the cell, are called exosomes (see [26] for more details about MVEs)

Fig. 3

Role of exosomes in immune escape. This immune cell lineage groups cell types in dashed boxes that are commonly classified as myeloid cells or white blood cells. Highlighted in red with asterisks are the immune escape mechanisms conferred to each immune cell type by tumor-derived exosomes (functions from [–81])