Exosomal Leucine-Rich-Alpha2-Glycoprotein 1 Derived from Non-Small-Cell Lung Cancer Cells Promotes Angiogenesis via TGF-β Signal Pathway

Li, Zifan; Zeng, Chao; Nong, Qiaohong; Long, Feihu; Liu, Jixian; Mu, Zhimin; Chen, Baokun; Wu, Der-Min; Wu, Hao

doi:10.1016/j.omto.2019.08.001

Cited by 52 publications

(35 citation statements)

References 25 publications

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“…Our previous work demonstrated that LRG1 significantly accelerated diabetic kidney injury and TGF-β/ALK1-induced angiogenesis in an experimental model of early diabetic kidney disease [6]. Consistently, LRG1 promotes angiogenesis by modulating endothelial TGF-β signaling in retinal vascular [5] and NSCLC [22]. LRG1 can also modulate the invasion and migration of glioma cell lines through the TGF-β signaling pathway [23].…”

Section: Discussionmentioning

confidence: 79%

LRG1 May Accelerate the Progression of ccRCC via the TGF-β Pathway

Hong

Wang

Liu

et al. 2020

BioMed Research International

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Clear cell renal cell carcinoma (ccRCC) accounts for 60-70% of renal cell carcinoma (RCC) cases. It is an urgent mission to find more therapeutic targets for advanced ccRCC. Leucine-rich a-2-glycoprotein 1 (LRG1) is a secreted protein associated with a variety of malignancies. Our study focused on the expression and mechanism of LRG1 in ccRCC based on data from The Cancer Genome Atlas (TCGA) and provided primary verification including LRG1 expression detection, LRG1 gene methylation detection, and downstream signaling detection. We found that LRG1 was overexpressed in ccRCC kidney tissue samples, and the methylation level of LRG1 gene was significantly decreased in ccRCC. Moreover, the expression of LRG1 was negatively related to patient survival. Based on our previous study and the verification reported in this article, we propose that demethylation-induced overexpression of LRG1 is likely to accelerate ccRCC progression via the TGF-β pathway.

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Section: Discussionmentioning

confidence: 79%

LRG1 May Accelerate the Progression of ccRCC via the TGF-β Pathway

Hong

Wang

Liu

et al. 2020

BioMed Research International

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“…The importance of exosomes in governing various physiological and pathological conditions is no longer in doubt. Exosomes may transfer signals to induce EMT, cell migration and invasion, angiogenesis, and metastasis processes [ 5 , 8 , 9 , 10 , 11 ]. It should be noted that the majority of studies were performed with exosomes from cell culture.…”

Section: Discussionmentioning

confidence: 99%

Total Blood Exosomes in Breast Cancer: Potential Role in Crucial Steps of Tumorigenesis

Konoshenko

Sagaradze

Orlova

et al. 2020

IJMS

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Exosomes are crucial players in cell-to-cell communication and are involved in tumorigenesis. There are two fractions of blood circulating exosomes: free and cell-surface-associated. Here, we compared the effect of total blood exosomes (contain plasma exosomes and blood cell-surface-associated exosomes) and plasma exosomes from breast cancer patients (BCPs, n = 43) and healthy females (HFs, n = 35) on crucial steps of tumor progression. Exosomes were isolated by ultrafiltration, followed by ultracentrifugation, and characterized by cryo-electron microscopy (cryo-EM), nanoparticle tracking analysis, and flow cytometry. Cryo-EM revealed a wider spectrum of exosome morphology with lipid bilayers and vesicular internal structures in the HF total blood in comparison with plasma. No differences in the morphology of both exosomes fractions were detected in BCP blood. The plasma exosomes and total blood exosomes of BCPs had different expression levels of tumor-associated miR-92a and miR-25-3p, induced angiogenesis and epithelial-to-mesenchymal transition (EMT), and increased the number of migrating pseudo-normal breast cells and the total migration path length of cancer cells. The multidirectional effects of HF total blood exosomes on tumor dissemination were revealed; they suppress the angiogenesis and total migration path length of MCF10A, but stimulate EMT and increase the number of migrating MCF10A and the total path length of SKBR3 cells. In addition, HF plasma exosomes enhance the metastasis-promoting properties of SKBR3 cells and stimulate angiogenesis. Both cell-free and blood cell-surface-associated exosomes are involved in the crucial stages of carcinogenesis: the initiation of EMT and the stimulation of proliferation, cell migration, and angiogenesis. Thus, for the estimation of the diagnostic/prognostic significance of circulating exosomes in the blood of cancer patients more correctly, the total blood exosomes, which consist of plasma exosomes and blood cell-surface-associated exosomes should be used.

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“…These vesicular structures are highly stable and are small enough to penetrate into and interact with different tissues. Exosomes are involved in key physiological processes such as cell-to-cell communications [3], proliferation [4], migration [5], invasion [6], angiogenesis [7], and tumor growth [8] through the horizontal transfer of RNA and proteins.…”

Section: Introductionmentioning

confidence: 99%

Proteomic Analysis of Blood Exosomes from Healthy Females and Breast Cancer Patients Reveals an Association between Different Exosomal Bioactivity on Non-tumorigenic Epithelial Cell and Breast Cancer Cell Migration in Vitro

et al. 2020

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Exosomes are important intercellular communication vehicles, secreted into body fluids by multiple cell types, including tumor cells. They contribute to the metastatic progression of tumor cells through paracrine signalling. It has been recently discovered that blood circulating exosomes contain distinguishable fractions of free and cell-surface-associated vesicles. We evaluated the influence of protein cargoes from exosomes from plasma, and exosomes from the total blood of healthy females (HFs) and breast cancer patients (BCPs), on cell motility. We conducted a mass spectrometric analysis of exosomal contents isolated from samples using ultrafiltration and ultracentrifugation approaches and verified their nature using transmission electron microscopy, nanoparticle tracking analysis and flow cytometry. We observed that malignant neoplasm-associated proteins in exosomes from BCP total blood were detected more often than in plasma (66% vs. 59%). FunRich analysis to assess Gene Ontology (GO) enrichment revealed that proteins with catalytic activities, transporter functions and protein metabolism activities were increased in exosomes from BCP blood. Finally, GO analysis revealed that proteomic profiles of exosomes from HF total blood were enriched with proteins inhibiting cell migration and invasion, which explains the low stimulating activity of exosomes from HF total blood on SKBR-3 cancer cell migration velocity. This allows exosomes to act as intermediaries providing intercellular communications through horizontal transfer of RNA and functionally active proteins, potentially affecting the development of both primary neoplasms and distant metastases.

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Exosomal Leucine-Rich-Alpha2-Glycoprotein 1 Derived from Non-Small-Cell Lung Cancer Cells Promotes Angiogenesis via TGF-β Signal Pathway

Cited by 52 publications

References 25 publications

LRG1 May Accelerate the Progression of ccRCC via the TGF-β Pathway

LRG1 May Accelerate the Progression of ccRCC via the TGF-β Pathway

Total Blood Exosomes in Breast Cancer: Potential Role in Crucial Steps of Tumorigenesis

Proteomic Analysis of Blood Exosomes from Healthy Females and Breast Cancer Patients Reveals an Association between Different Exosomal Bioactivity on Non-tumorigenic Epithelial Cell and Breast Cancer Cell Migration in Vitro

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