Exosomes, derived from multivesicular bodies, exhibit a cup-shaped under electron microscopy, with diameters ranging from 50 to 150 nanometers. Loaded with various contents, including nucleic acids, proteins, lipids, enzymes and metabolites. These contents can indicate the physiological status of the exosome-derived cells and have gradually found applications in the diagnosis and treatment of diseases. In recent years, exosomal proteins have attracted increasing attention from researchers, and a plethora of studies have emerged regarding their role in tumor initiation, development, cancer diagnosis, and treatment.
A recent review titled “The updated role of exosomal proteins in the diagnosis, prognosis, and treatment of cancer,” published in Experimental & Molecular Medicine, summarizes the impact of exosomal proteins on tumor initiation and development. It emphasizes their diagnostic and prognostic roles in various cancers and explores the potential applications of exosomal proteins in cancer treatment.
Exosome proteins can be wrapped in the membrane or embedded on the exosome surface, allowing the categorization of exosomes based on membrane proteins. For example, certain proteins like CD63, TSG101, and Alix are considered positive markers, while others like Calnexin are considered negative markers. Additionally, exosome membrane proteins are involved in the synthesis, guidance and interaction of exosomes.
Table 1. Exosome Membrane Proteins and Their Functions
Exosomes, as a crucial form of communication between tumor cells and non-tumor cells in the microenvironment, play a significant role in various aspects of tumor development. Exosomal proteins contribute significantly to cancer in areas such as epithelial-to-mesenchymal transition, extracellular matrix remodeling, angiogenesis, tumor-related immune regulation, pre-metastatic behavior, and tumor drug resistance.
Figure 1. Cellular Biological Functions of Exosomal Proteins
Exosome proteins obtained from body fluids (plasma, serum, urine and pleural effusion), tumor tissues and cell lines serve as specific diagnostic and prognostic factors for various cancers, including breast cancer, bladder cancer, lung cancer, gastric cancer, liver cancer, colorectal cancer, ovarian cancer, thyroid cancer, and pancreatic cancer. The expression profiles of exosomal proteins often show significant differences across different cancer types and stages, indicating a close association with cancer occurrence and development.
Figure 2. Exosomal Protein Biomarkers in Various Tumors
Due to the immature state of technologies for identifying and isolating specific exosomal subgroups, exploring the impact of exosome-mediated transport on drug delivery remains challenging. Researchers currently believe that designing exosomes carrying targeting ligands and stimulus-response factors may facilitate the application of exosomes in cancer treatment. Exosomes can be modified by changing internal proteins (adding proteins to the source cell or exosome) and changing surface proteins (adding proteins to the membrane of the source cell or exosome). Exosomes containing tumor antigens can stimulate antigen-presenting cells and drive the body’s anti-tumor immune response. Artificially designed exosomes can also directly release anti-tumor proteins to attack tumor cells.
Figure 3. Modification of Proteins and Membrane Proteins with Exosomes
In summary, exosomal proteins or proteomic profiling can not only provide diagnostic and prognostic clues for cancer patients, but also hold promise for future cancer treatment. In addition, to effectively integrate the research findings from different teams and translate the feasibility of exosome application into clinical reality, there is an urgent need to standardize methods for the isolation and identification of exosomes.
Reference:
Wang X, Huang J, Chen W, Li G, Li Z, Lei J. The updated role of exosomal proteins in the diagnosis, prognosis, and treatment of cancer. Exp Mol Med. 2022;54(9):1390-1400. doi:10.1038/s12276-022-00855-4
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