Abstract
Simple SummaryExosomes (or extracellular vesicles) are known to mediate intercellular communication and to transmit molecular signals between cells. Molecules carried by exosomes have their own molecular roles in affecting surrounding and distant environment, as well as recipient cells. Molecular components of exosomes can be used as cancer biomarkers for diagnosis and prognosis, being promising therapeutic targets for the interruption of cellular signals. Therefore, the understanding of the molecular compositions and their functional indications of exosomes has the potential to help doctors to diagnose and monitor diseases and to allow researchers to design and develop potential targeted therapies. This review aims to provide a comprehensive protein and lipid characterization of lung cancer exosomes and to explore their molecular functions and mechanisms regulating physiological and pathological processes. This organization offers informative insight for lung cancer diagnosis and treatment.Exosomes participate in cell–cell communication by transferring molecular components between cells. Previous studies have shown that exosomal molecules derived from cancer cells and liquid biopsies can serve as biomarkers for cancer diagnosis and prognosis. The exploration of the molecules transferred by lung cancer-derived exosomes can advance the understanding of exosome-mediated signaling pathways and mechanisms. However, the molecular characterization and functional indications of exosomal proteins and lipids have not been comprehensively organized. This review thoroughly collected data concerning exosomal proteins and lipids from various lung cancer samples, including cancer cell lines and cancer patients. As potential diagnostic and prognostic biomarkers, exosomal proteins and lipids are available for clinical use in lung cancer. Potential therapeutic targets are mentioned for the future development of lung cancer therapy. Molecular functions implying their possible roles in exosome-mediated signaling are also discussed. Finally, we emphasized the importance and value of lung cancer stem cell-derived exosomes in lung cancer therapy. In summary, this review presents a comprehensive description of the protein and lipid composition and function of lung cancer-derived exosomes for lung cancer diagnosis, prognosis, and treatment.
Highlights
As the studies of exosomal microRNAs and long noncoding RNAs in lung cancer have been organized in other reviews [55–60], this review focuses on the studies of the proteins and lipids in lung cancer-derived exosomes
We summarized the proteins that were identified in exosomes from lung cancer cell lines and patient biopsies, including plasma, serum, urine, saliva, bronchoalveolar lavage (BAL) fluid, pleural effusion, pericardial effusion, and tumor tissue
This study showed that the exosomal lipid-based classification models were mainly composed of lipid classes of PC, SM, cholesterol esters (CE), triacylglyceride (TAG), and lysophosphatidylcholine (LysoPC) (Table 3), implying that these lipid classes were found and detected in exosomes from lung cancer samples and that the lipid features could be lipid biomarkers for the discrimination between lung cancer patients and healthy individuals
Summary
Extracellular vesicles (EVs) and exosomes mediate cell–cell communication within the tumor microenvironment and regulate signaling pathways in their target cells [1,2]. Several reviews have discussed the potential applications and importance of EVs and exosomes in the fields of various cancers and tumors (e.g., lung [20], liver [21], pancreatic [22], colorectal [23], gastric [24], kidney [25], bladder [26], prostate [27], breast [28], ovarian [29], cervical [30], head and neck [31], thyroid [32], glioma [33], melanoma [34], and hematological malignancies [35]), neurodegenerative diseases (e.g., Alzheimer’s disease [36], Parkinson’s disease [37], Huntington’s disease [38], and amyotrophic lateral sclerosis [39]), mental disorders [40], cardiovascular diseases [41], diabetes mellitus [42,43], and inflammatory and autoimmune diseases [44] These numerous studies have provided great insights into the diagnostic and therapeutic applications of exosomes in a wide spectrum of diseases. Several studies of exosomes in lung cancer have been discussed from multiple perspectives, including the topics of experimental methods and techniques of isolation and characterization, biogenesis and secretion, molecular composition and function, communicative roles within the tumor microenvironment, effect and impact on tumor progression, and clinical applications in cancer therapy, among other perspectives [20,47–54]. This study will help to establish a detailed overview of exosome-mediated tumor progression and other pathological processes
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