Abstract
Exosomes are a subset of extracellular vesicles that carry specific combinations of proteins, nucleic acids, metabolites, and lipids. Mounting evidence suggests that exosomes participate in intercellular communication and act as important molecular vehicles in the regulation of numerous physiological and pathological processes, including cancer development. Exosomes are released by various cell types under both normal and pathological conditions, and they can be found in multiple bodily fluids. Moreover, exosomes carrying a wide variety of important macromolecules provide a window into altered cellular or tissue states. Their presence in biological fluids renders them an attractive, minimally invasive approach for liquid biopsies with potential biomarkers for cancer diagnosis, prediction, and surveillance. Due to their biocompatibility and low immunogenicity and cytotoxicity, exosomes have potential clinical applications in the development of innovative therapeutic approaches. Here, we summarize recent advances in various technologies for exosome isolation for cancer research. We outline the functions of exosomes in regulating tumor metastasis, drug resistance, and immune modulation in the context of cancer development. Finally, we discuss prospects and challenges for the clinical development of exosome-based liquid biopsies and therapeutics.
Highlights
Exosomes, which are secreted by multiple cell types, are a subtype of extracellular vesicles (EVs) that range in size from approximately 40 to 160 nm in diameter [1]
In the last decade, there has been a substantial increase in the number of studies aimed at understanding the biology and function of exosomes in disease, especially cancer [291]
These studies established that exosomes are associated with several cancer hallmarks that influence tumor metastasis, immune modulation, and resistance to therapy [7]
Summary
Exosomes, which are secreted by multiple cell types, are a subtype of extracellular vesicles (EVs) that range in size from approximately 40 to 160 nm in diameter [1]. Compared with the classical UC protocol, ultrafiltration techniques provide a higher particle yield, thereby increasing exosome yield and isolation efficiency with a shorter processing time While these size-based techniques have been widely used in many fields, they still require a relatively long running time, limiting their usefulness in treatment and research. Another study reported that triple-negative breast cancer (TNBC) cells can activate stromal cells by releasing exosomes containing unshielded RNAs that mimic viral components to co-opt anti-viral immune responses, thereby promoting tumor growth [115]. Several cell types in tumor microenvironments, e.g., macrophages and CAFs, have been shown to play key roles in cancer metastasis via exosomes. EGFR carried in exosomes secreted from gastric cancer cells can be delivered to the liver and integrated into the plasma membrane of liver stromal cells, favoring the development of a liver-like microenvironment and promoting liver-specific metastasis [147]. Via a proteomic analysis of EVs and other particles, including exosomes, from 426 human samples, David Lyden’s team found that pan-EVs and particles can carry cargo that can be used to classify ambiguous primary tumor types
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