Hepatoma cell‐secreted exosomal microRNA‐103 increases vascular permeability and promotes metastasis by targeting junction proteins

Fang, Jian; Zhang, Mengjie; Shang, Li Ru; Luo, Yu; Lin, Yi; Yuan, Yunfei; Zhuang, Shi‐Mei

doi:10.1002/hep.29920

Cited by 263 publications

(198 citation statements)

References 37 publications

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“…In this scenario, exosomal miRNAs seem to play relevant roles as metastasis-promoting factors. In HCC, the high levels of serum miR-103a-3p are associated with patients with metastasic episodes [102]. This exosomal miRNA, released by liver cancer cells, is able to attenuate the junction integrity of recipient endothelial cells (HUVEC) by targeting adhesion molecules such as VE-cad, p120, and zonula occludens 1 (ZO-1), thus increasing the vascular permeability both in vivo and in vitro [102].…”

Section: The Cellular Crosstalk In the Tumor Microenvironment Promotementioning

confidence: 99%

“…In HCC, the high levels of serum miR-103a-3p are associated with patients with metastasic episodes [102]. This exosomal miRNA, released by liver cancer cells, is able to attenuate the junction integrity of recipient endothelial cells (HUVEC) by targeting adhesion molecules such as VE-cad, p120, and zonula occludens 1 (ZO-1), thus increasing the vascular permeability both in vivo and in vitro [102]. The subsequent tumor cell transendothelial motility process is promoted by exosomal miR-25-5p [103].…”

Section: The Cellular Crosstalk In the Tumor Microenvironment Promotementioning

confidence: 99%

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The Crosstalk between Tumor Cells and the Microenvironment in Hepatocellular Carcinoma: The Role of Exosomal microRNAs and Their Clinical Implications

Pascut

Pratama

Võ

et al. 2020

Cancers

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The communication between hepatocellular carcinoma (HCC) cells and their microenvironment is an essential mechanism supporting or preventing tumor development and progression. Recent evidence has identified extracellular vesicles (EVs) as one of the mechanisms mediating paracrine signaling between cells. Exosomes, the most described class of EVs, deliver proteins, mRNAs, noncoding RNAs, DNA, and lipids to recipient cells, also at remote distances. MicroRNAs (miRNAs), as part of the non-coding RNA exosomal cargo, have an important role in regulating cellular pathways in targeted cells, regulating several processes related to tumor progression invasion and metastasis, such as angiogenesis, immune-escape, epithelial-to-mesenchymal transition, invasion, and multi-drug resistance. Accumulating evidence suggests exosomal miRNAs as relevant players in the dynamic crosstalk among cancerous, immune, and stromal cells in establishing the tumorigenic microenvironment. In addition, they sustain the metastasic niche formation at distant sites. In this review, we summarized the recent findings on the role of the exosome-derived miRNAs in the cross-communication between tumor cells and different hepatic resident cells, with a focus on the molecular mechanisms responsible for the cell re-programming. In addition, we describe the clinical implication derived from the exosomal miRNA-driven immunomodulation to the current immunotherapy strategies and the molecular aspects influencing the resistance to therapeutic agents.

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Section: The Cellular Crosstalk In the Tumor Microenvironment Promotementioning

confidence: 99%

Section: The Cellular Crosstalk In the Tumor Microenvironment Promotementioning

confidence: 99%

The Crosstalk between Tumor Cells and the Microenvironment in Hepatocellular Carcinoma: The Role of Exosomal microRNAs and Their Clinical Implications

Pascut

Pratama

Võ

et al. 2020

Cancers

View full text Add to dashboard Cite

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“…Angiogenesis is also valuable in accelerating HCC proliferation. Fang et al . sequenced and quantitated PCR and found that HCC cell‐derived exosomes transmitted miR‐103 into endothelial cells attenuated the endothelial junction integrity by downregulating VE‐Cadherin (VE‐Cad), p120‐catenin (p120) and zonula occludens 1 (Table ).…”

Section: Exosome and Tumor Developmentmentioning

confidence: 99%

“…Angiogenesis is also valuable in accelerating HCC proliferation. Fang et al 53 sequenced and quantitated PCR and found that HCC cell-derived exosomes transmitted miR-103 into endothelial cells attenuated the endothelial junction integrity by downregulating VE-Cadherin (VE-Cad), p120-catenin (p120) and zonula occludens 1 (Table 1). Also, there is emerging evidence indicating that HCC-derived exosomal miR-21 targeting PTEN led to the activation of PDK1/AKT signaling in HSCs, which educated CAFs released angiogenic cytokines, including VEGF, MMP2, MMP9, bFGF and TGF-beta (Table 1).…”

Section: Cancer Metastasismentioning

confidence: 99%

The cancer exosomes: Clinical implications, applications and challenges

Tang

Hou

et al. 2019

Intl Journal of Cancer

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The exosome is a small functional vesicle enriched in selected proteins, lipids and nucleic acids, displaying distinct molecular heterogeneity. Exosomes released can transform the extracellular matrix microenvironments, transmit signals and molecules to recipient cells and trigger changes in their pathophysiological functions. Tumor‐derived exosomes mediate the interactions of tumor cells and microenvironment significantly, and they stimulate tumor growth and development through specific signaling pathways related to metastasis, therapeutic resistance and immunosuppression. Exosome biogenesis from tumors often represents abundant biological information, and novel and efficient isolation and detection methods of exosomes provide a promising approach for tumor diagnosis and prognosis estimation. Moreover, exosome can even be developed as therapeutic agents for multiple disease models based on effective material transport characteristics and biofilm specificity. This review reports the clinical implications and challenges of exosomes in cancer progression, therapy resistance, metastasis and immune escape, and underlying cancerogenic pathological phenotypes including fibrosis and viral infection.

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“…Hepatocellular carcinoma (HCC) cells use EV for the transfer of miRNA, long non‐coding RNA (lncRNA) and protein factors implicated in cancer development, migration and chemotherapy resistance to other HCC cells, to hepatocytes but also to endothelial cells and to fibroblasts . Fang et al reported that metastatic HCC cell lines (MHCC97H and QGY‐7703) exhibited increased production of EV containing miRNA‐103, identified as exosomes; when transferred to endothelial cells (LSEC, SK‐Hep‐1 and HUVEC), these EV increased in vitro the permeability of endothelial cell monolayers and reduced cell junctions integrity by a an interference with VE‐cadherin, p120 and ZO‐1 proteins . Interfering with exosome trafficking or using miRNA‐103 inhibitor RNA alleviated the effect of these EV on endothelial cells.…”

Section: Extracellular Vesicles In Chronic Liver Diseasesmentioning

confidence: 99%

Extracellular vesicles: Future diagnostic and therapeutic tools for liver disease and regeneration

Balaphas

Meyer

Sadoul

et al. 2019

Liver International

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Extracellular vesicles are membrane fragments that can be produced by all cell types. Interactions between extracellular vesicles and various liver cells constitute an emerging field in hepatology and recent evidences have established a role for extracellular vesicles in various liver diseases and physiological processes. Extracellular vesicles originating from liver cells are implicated in intercellular communication and fluctuations of specific circulating extracellular vesicles could constitute new diagnostic tools. In contrast, extracellular vesicles derived from progenitor cells interact with hepatocytes or non‐parenchymal cells, thereby protecting the liver from various injuries and promoting liver regeneration. Our review focuses on recent developments investigating the role of various types of extracellular vesicles in acute and chronic liver diseases as well as their potential use as biomarkers and therapeutic tools.

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Hepatoma cell‐secreted exosomal microRNA‐103 increases vascular permeability and promotes metastasis by targeting junction proteins

Abstract: Hepatoma cell-secreted exosomal miR-103 increases vascular permeability and promotes tumor metastasis by targeting multiple endothelial junction proteins, which highlights secreted miR-103 as a potential therapeutic target and a predictive marker for HCC metastasis. (Hepatology 2018).

Cited by 263 publications

References 37 publications

The Crosstalk between Tumor Cells and the Microenvironment in Hepatocellular Carcinoma: The Role of Exosomal microRNAs and Their Clinical Implications

The Crosstalk between Tumor Cells and the Microenvironment in Hepatocellular Carcinoma: The Role of Exosomal microRNAs and Their Clinical Implications

The cancer exosomes: Clinical implications, applications and challenges

Extracellular vesicles: Future diagnostic and therapeutic tools for liver disease and regeneration

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