Roles of exosomes in the carcinogenesis and clinical therapy of non-small cell lung cancer

Liu, Sile; Zhan, Yuting; Luo, Jianmin; Feng, Juan; Lu, Junmi; Zheng, Hongmei; Wen, Qiuyuan; Fan, Songqing

doi:10.1016/j.biopha.2018.12.088

Cited by 47 publications

(28 citation statements)

References 130 publications

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“…The EVs may contribute to various cellular functions, including epithelial-mesenchymal transition, angiogenesis, tumorigenesis and metastasis associated with lung cancer [202,203]. Further, exosome secretion and release within the tumor microenvironment changes the levels of cytokines and growth factors such as TGF-β, IL-10, IL-6, MCP-1 by activation of proliferative signaling cascades like MAP kinases and NF-KB pathways and are therefore instrumental in promoting lung tumor progression and metastasis [204][205][206].…”

Section: Lung Cancermentioning

confidence: 99%

Extracellular vesicles: novel communicators in lung diseases

et al. 2020

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The lung is the organ with the highest vascular density in the human body. It is therefore perceivable that the endothelium of the lung contributes significantly to the circulation of extracellular vesicles (EVs), which include exosomes, microvesicles, and apoptotic bodies. In addition to the endothelium, EVs may arise from alveolar macrophages, fibroblasts and epithelial cells. Because EVs harbor cargo molecules, such as miRNA, mRNA, and proteins, these intercellular communicators provide important insight into the health and disease condition of donor cells and may serve as useful biomarkers of lung disease processes. This comprehensive review focuses on what is currently known about the role of EVs as markers and mediators of lung pathologies including COPD, pulmonary hypertension, asthma, lung cancer and ALI/ARDS. We also explore the role EVs can potentially serve as therapeutics for these lung diseases when released from healthy progenitor cells, such as mesenchymal stem cells. Extracellular vesicles Cell-to-cell communication is essential for nearly all physiologic and metabolic processes. This intercellular conveyance is achieved through receptor ligands, signaling molecules, hormones, and extracellular vesicles (EVs). Historically, secretion of the cell in the form of EVs was considered as unimportant waste material, cellular "garbage bags," or dust particles [1-5]. However, in recent years, this so-called "waste" is now known to be of profound importance in various biological systems, creating a boon in their exploration across the scientific community. Lipid bilayer membrane-enclosed vesicles are secreted by both prokaryotic and eukaryotic cells [4-9]. Although, the term "extracellular vesicle" is sometimes used in reference to exosomes, it is actually a very broad term that encompasses all different types of vesicles secreted outside the cells [10]. Regardless, the function of all these vesicles appears to be all the same: communication between the cells within an organism or between species [11, 12]. In addition, it is not necessary that all vesicles secreted from cells are functional or have any role in some kind of biological process. Sometimes, they just act as "dustcart" to remove the waste from cells [13]. Of note, there have been discrepancies in the classification of these vesicles in the literature. Some studies divide EVs into two major categories: I) exosomes, defined as vesicles released by exocytosis of the multivesicular bodies; and II) ectosomes, defined as the vesicles which are assembled and released by the plasma membrane [14]. However, most recent studies categorize EVs as either exosome, microvesicles, microparticles, or apoptotic bodies based on vesicle size and how they are formed [15-21] (Fig. 1). Exosomes Exosomes are small EVs with sizes ranging between 30 and 150 nm in diameter that originate from the internal vesicles of multivesicular bodies (MVB) of nearly all cell types. Exosomes originating from different cell types have different composition; however, there are certain

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Section: Lung Cancermentioning

confidence: 99%

Extracellular vesicles: novel communicators in lung diseases

et al. 2020

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“…Whatever their dimension, exosomes have an active role in the process of carcinogenesis, progression, and metastasis of several tumors, including NSCLC, which is exerted by transferring their cargo. For instance, exosomes can promote angiogenesis by transferring proteins such as fibroblast growth factor (FGF), vascular endothelial growth factor (VEGF), IL-6, and IL-8, and by stimulating vascular endothelial cells via miRNAs [79,80]. Yongjian and colleagues demonstrated that miR-660-5p, a miRNA known for its role in the progression of breast cancer, is also expressed at high levels in NSCLC patients both in exosomes and in blood plasma, compared with healthy controls.…”

Section: Exosomesmentioning

confidence: 99%

Liquid Biopsy in Non-Small Cell Lung Cancer: Highlights and Challenges

Rijavec

Coco

Genova

et al. 2019

Cancers

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Non-small cell lung cancer is one leading cause of death worldwide, and patients would greatly benefit from an early diagnosis. Since targeted and immunotherapies have emerged as novel approaches for more tailored treatments, repeated assessments of the tumor biology have become pivotal to drive clinical decisions. Currently, tumor tissue biopsy is the gold standard to investigate potentially actionable biomarkers, but this procedure is invasive and may prove inadequate to represent the whole malignancy. In this regard, liquid biopsy represents a minimally invasive and more comprehensive option for early detection and investigation of this tumor. Today, cell-free DNA is the only approved circulating marker to select patients for a targeted therapy. Conversely, the other tumor-derived markers (i.e., circulating tumor cells, miRNAs, exosomes, and tumor educated platelets) are still at a pre-clinical phase, although they show promising results for their application in screening programs or as prognostic/predictive biomarkers. The main challenges for their clinical translation are the lack of reliable cutoffs and, especially for miRNAs, the great variability among the studies. Moreover, no established tool has been approved for circulating tumor cells and exosome isolation. Finally, large prospective clinical trials are mandatory to provide evidence of their clinical utility.

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“…In this context, the MVBs, which fuse with lysosomes, display specific surface proteins, including tumor suppressor. His domain contains protein tyrosine phosphatase (HD-PTP), the HOP complex (HSP70-HSP90 proteins), the GTPase Ras-related protein Rab7A, and members of the membrane fusion proteins SNARE complex (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) such as VAMP7 (vesicle-associated membrane protein 7), STX7 (syntaxin 7), and STX8 (syntaxin 8) [35]. The MVBs are integrated into the endosomal recycling system, where MVBs traffic and fuse with the cell membrane to release the exosomes in extracellular spaces.…”

Section: Exosomes Biogenesismentioning

confidence: 99%

A Comprehensive Picture of Extracellular Vesicles and Their Contents. Molecular Transfer to Cancer Cells

Jurj

Zănoagă

Braicu

et al. 2020

Cancers

105

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Critical processes such as growth, invasion, and metastasis of cancer cells are sustained via bidirectional cell-to-cell communication in tissue complex environments. Such communication involves the secretion of soluble factors by stromal cells and/or cancer cells within the tumor microenvironment (TME). Both stromal and cancer cells have been shown to export bilayer nanoparticles: encapsulated regulatory molecules that contribute to cell-to-cell communication. These nanoparticles are known as extracellular vesicles (EVs) being classified into exosomes, microvesicles, and apoptotic bodies. EVs carry a vast repertoire of molecules such as oncoproteins and oncopeptides, DNA fragments from parental to target cells, RNA species (mRNAs, microRNAs, and long non-coding RNA), and lipids, initiating phenotypic changes in TME. According to their specific cargo, EVs have crucial roles in several early and late processes associated with tumor development and metastasis. Emerging evidence suggests that EVs are being investigated for their implication in early cancer detection, monitoring cancer progression and chemotherapeutic response, and more relevant, the development of novel targeted therapeutics. In this study, we provide a comprehensive understanding of the biophysical properties and physiological functions of EVs, their implications in TME, and highlight the applicability of EVs for the development of cancer diagnostics and therapeutics.

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Roles of exosomes in the carcinogenesis and clinical therapy of non-small cell lung cancer

Cited by 47 publications

References 130 publications

Extracellular vesicles: novel communicators in lung diseases

Extracellular vesicles: novel communicators in lung diseases

Liquid Biopsy in Non-Small Cell Lung Cancer: Highlights and Challenges

A Comprehensive Picture of Extracellular Vesicles and Their Contents. Molecular Transfer to Cancer Cells

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