Emerging Role of Exosomes in Liquid Biopsy for Monitoring Prostate Cancer Invasion and Metastasis

Abstract

Prostate cancer (PCa) is the most common solid tumor in men. While patients with local PCa have better prognostic survival, patients with metastatic PCa have relatively high mortality rates. Existing diagnostic methods for PCa rely on tissue biopsy and blood prostate-specific antigen (PSA) detection; however, the PSA test does not detect aggressive PCa. Liquid biopsy is a promising technique to overcome tumor heterogeneity in diagnosis, provide more comprehensive information, and track tumor progression over time, allowing for the development of treatment options at all stages of PCa. Exosomes containing proteins and nucleic acids are potential sources of tumor biomarkers. Accumulating evidence indicates that exosomes play important roles in cell communication and tumor progression and are suitable for monitoring PCa progression and metastasis. In this review, we summarize recent advances in the use of exosomal proteins and miRNAs as biomarkers for monitoring PCa invasion and metastasis and discuss their feasibility in clinical diagnosis.

Keywords: biomarker; exosome; invasion and metastasis; liquid biopsy; prostate cancer.

FIGURE 1

Exosome biogenesis. (1) Exosome: The cytoplasmic membrane endocytosis to form vesicles, which are then fused with early endosomes. Then, the early endosomes invade to form multivesicular bodies (MVBs). Finally, MVBs are fused with cell membranes and released outside the cell to become exosomes. Diameter: 30∼120 nm. (2) Microvesicles: Budding directly from the cell membrane. Diameter: 100 nm∼1 μm (3) Apoptotic bodies: Released when cells suffer from programmed death or late apoptosis. Diameter: 500 nm∼2 μm.

FIGURE 2

Role of exosomes in the invasion and metastasis of PCa. (1) The exosomes secreted by PCa bind to the components of ECM through adhesion receptors and released proteases, which makes the ECM reshape and be hydrolyzed by enzymes. In addition, in PCa, exosomes promote epithelial cells to mesenchymal cells. This allows cancer cells to invade the tissue barrier and metastasize. (2) In PCa, exosomes promote angiogenesis by transferring sphingomyelin and CD147 to endothelial cells; in the case of hypoxia, exosomes promote angiogenesis by promoting the secretion of angiogenic factors. (3) PCa cell-derived exosomes induce the Warburg effect, increase glycolysis rate, and produce lactic acid in stromal cells, leading to cancer progression and invasion. (4) In the tumor microenvironment, cancer cells remodel B cells, T cells, DCs, and NK cells via exosomes to promote tumor progression. EMT, epithelial–mesenchymal transition; FGF, fibroblast growth factor; FGFR, fibroblast growth factor receptor; MMP, matrix metalloproteinase; VEGF, vascular endothelial grown factor; VEGFR, vascular endothelial growth factor receptor.

FIGURE 3

Analysis of exosomes in liquid biopsy of PCa. High concentrations of exosomes are found in various body fluids, including blood, urine, saliva, and seminal plasma. The proteins and RNAs enriched in exosomes reflect the specific physiological conditions and functions of their samples. These exosomes and their biomolecules are ideal biomarkers for liquid biopsy.