Exosomes: The Indispensable Messenger in Tumor Pathogenesis and the Rising Star in Antitumor Applications

Abstract

understanding of the underlying interaction mechanisms between tumor cells and the TME, as well as derivative tumor treatment strategies, is of great significance for oncology and diagnostic development.Exosomes represent a kind of nanosized (30-150 nm) lipid bilayer membrane vesicles that are naturally secreted by almost all types of cells and exist widely in various body fluids, such as plasma, [4] saliva, [5] perspiration, urine, [6] latex, cerebrospinal fluid, nasal mucus, and ascites. After their discovery in 1983, exosomes were widely considered as useless "cellular waste" for a long time. [7] In 1996, Raposo et. al. [8] demonstrated that exosomes derived from human and murine B lymphocytes could transfer antigen and induce antigen-specific T cell responses, which discovery changed the "cellular waste concept" of exosomes. Renewed interest in exosomes followed recent reports demonstrating that exosomes contribute to various aspects of cellular homeostasis, physiology and pathobiology. [9] Intercellular communication is considered as one of the most fascinating roles of exosomes. [10] As the intercellular vehicles to transport message, exosomes inherit various molecular information (including proteins, nucleic acids, lipids) from the origin cell and reflect the phenotypic state. Moreover, these biological entities subsequently affect physiological and pathological processes such as inflammation, immune surveillance, tumorigenesis. [11] As important parts of the tumor microenvironment (TME), exosomes have been widely investigated in past decades and demonstrated to possess specialized functions in tumor initiation, progression, metastasis, angiogenesis, and drug resistance. [12,13] Moreover, the specific molecular signature inherited from the origin tumor cell endow tumor-derived exosomes with the capacity to predict tumor progression and prognosis. [14,15] On the other hand, immune cell-derived exosomes, such as DC-derived exosomes, NK-derived exosomes and M1 macrophage-derived exosomes, play vital roles in activating antitumor immune response, which properties endow these exosomes with promising potential in acting as tumor therapeutic vaccine. In addition, the vesicular biocompatibility, nanometer dimension size and biochemical properties make sophisticated exosomes a novel promising therapeutic nanoplatform in cancer. [16] In this review, efforts are made to provide a comprehensive and critical overview about recent advances in exosome-related research field, ranging from their biogenesis, secretion, isolation and biological function in tumor pathogenesis to their extensive antitumor applications.As natural secreted nanovesicles through the endolysosomal pathway, exosomes have attracted increasing attention over the past decades. An overwhelming number of studies have provided evidence for the intriguing roles that exosomes play in intercellular communication. They are widely involved in the transmission of biomolecule cargos between original cells and neighboring/distant cells in normal physiologica...

The Role of Exosomes and Their Applications in Cancer

“…Firstly, exosome concentrations are higher than CTCs, thus avoiding procedures that require large amounts of blood or urine. Secondly, exosomes have high stability in the circulation, whereas ctDNA is rapidly degraded in the bloodstream [3,100,101]. Thirdly, exosomes can be gained from nearly all kinds of body fluids, including blood, urine, saliva, amniotic fluid, cerebrospinal fluids, bile, ascites, tears, breast milk and semen [102,103].…”

“…Cell communication is also critical in specific pathological processes. Indeed, cancer cells need to cross-talk to each other, normal cells, and immune system to survive, proliferate and metastasize [3]. Exosomes have been extensively studied because of their fascinating biological roles in cell-to-cell communication.…”

“…As one of the most impactful components in the TME, exosomes have been demonstrated to possess specialized functions in tumor initiation, progression, metastasis, angiogenesis and drug resistance [3]. Through a series of natural cytokines and growth factors carried by exosomes, immune cells and lymphoid components of the TME, such as B and T lymphocytes, natural killer cells, and macrophages, could be activated or inhibited by exosome-related grow factors and cytokines, resulting in immunosuppression and tumor progression [5,6].…”

Non-coding RNAs in exosomes and adipocytes cause fat loss during cancer cachexia

“…In internal secretion, exosomes enter the blood and lymph fluid to bind to specific cells in circulation. They either anchor ligands through the surface membrane, or act on cells through receptor-mediated endocytosis [ 49 ].…”

Exosomes as Theranostic Targets: Implications for the Clinical Prognosis of Aggressive Cancers

“…Cell interaction is also vital in several diseases. To exist, reproduce, and spread, cancer cells require interaction with other health and immune cells ( Wang et al, 2019a ). Exosomes gained a lot of interest due to their cell-to-cell interaction property.…”