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Extracellular vesicles-mediated signaling in the osteosarcoma microenvironment: Roles and potential therapeutic targets.

ABSTRACT: Osteosarcoma (OS) is the most common non-hematologic malignant tumor of bone in children. It is usually characterized by a high risk of developing lung metastasis and poor prognosis. Extracellular vesicles (EVs) are cell-derived nanoparticles with a small size of 50-200?nm in diameter. As a communicator, the contents of the EVs secreted via either fusing with lysosomes for degradation and recycling or fusing with the cell plasma membrane into the extracellular environment, which play an important role in regulating the tumor microenvironment of OS and mediating the Wnt/?-catenin and TGF-? signalings. Increasing evidences suggest that EVs have significant role in OS growth, progression, metastasis and drug resistance. In this study, the roles of EVs in the physiology and pathogenesis of OS and the potential attractive therapeutic target for the treatment of OS were reviewed.

SUBMITTER: Lan M

PROVIDER: S-EPMC6111053 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Extracellular vesicles-mediated signaling in the osteosarcoma microenvironment: Roles and potential therapeutic targets.

Lan Min M Zhu Xiao-Ping XP Cao Zhi-Yuan ZY Liu Jia-Ming JM Lin Qing Q Liu Zhi-Li ZL

Journal of bone oncology 20180806

Osteosarcoma (OS) is the most common non-hematologic malignant tumor of bone in children. It is usually characterized by a high risk of developing lung metastasis and poor prognosis. Extracellular vesicles (EVs) are cell-derived nanoparticles with a small size of 50-200 nm in diameter. As a communicator, the contents of the EVs secreted via either fusing with lysosomes for degradation and recycling or fusing with the cell plasma membrane into the extracellular environment, which play an importan ...[more]

PMID: 30155405

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Project description:Myocardial infarction (MI) triggers a potent inflammatory response via the release of circulatory mediators, including extracellular vesicles (EVs) by damaged cardiac cells, necessary for myocardial healing. Timely repression of inflammatory response are critical to prevent and minimize cardiac tissue injuries, nonetheless, progression in this aspect remains challenging. The ability of EVs to trigger a functional response upon delivery of carried bioactive cargos, have made them clinically attractive diagnostic biomarkers and vectors for therapeutic interventions. Using label-free quantitative proteomics approach, we compared the protein cargo of plasma EVs between patients with MI and from patients with stable angina (NMI). We report, for the first time, the proteomics profiling on 252 EV proteins that were modulated with >1.2-fold after MI. We identified six up-regulated biomarkers with potential for clinical applications; these reflected post-infarct pathways of complement activation (Complement C1q subcomponent subunit A (C1QA), 3.23-fold change, p = 0.012; Complement C5 (C5), 1.27-fold change, p = 0.087), lipoprotein metabolism (Apoliporotein D (APOD), 1.86-fold change, p = 0.033; Apolipoprotein C-III (APOCC3), 2.63-fold change, p = 0.029) and platelet activation (Platelet glycoprotein Ib alpha chain (GP1BA), 9.18-fold change, p < 0.0001; Platelet basic protein (PPBP), 4.72-fold change, p = 0.027). The data have been deposited to the ProteomeXchange with identifier PXD002950. This novel biomarker panel was validated in 43 patients using antibody-based assays (C1QA (p = 0.005); C5 (p = 0.0047), APOD (p = 0.0267); APOC3 (p = 0.0064); GP1BA (p = 0.0031); PPBP (p = 0.0465)). We further present that EV-derived fibrinogen components were paradoxically down-regulated in MI, suggesting that a compensatory mechanism may suppress post-infarct coagulation pathways, indicating potential for therapeutic targeting of this mechanism in MI. Taken together, these data demonstrated that plasma EVs contain novel diagnostic biomarkers and therapeutic targets that can be further developed for clinical use to benefit patients with coronary artery diseases (CADs).

Dataset Information

Extracellular vesicles-mediated signaling in the osteosarcoma microenvironment: Roles and potential therapeutic targets.

Publications

Extracellular vesicles-mediated signaling in the osteosarcoma microenvironment: Roles and potential therapeutic targets.

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