Primary tumor-derived exosomes facilitate metastasis by regulating adhesion of circulating tumor cells via SMAD3 in liver cancer

Fu, Qihan; Zhang, Qi; Lou, Yiting; Yang, Jiaqi; Nie, Gang; Chen, Qi; Chen, Yiwen; Zhang, Jingying; Wang, Jianxin; Tao, Wei; Qin, Hao; Dang, Xiaowei; Bai, Xueli; Liang, Tingbo

doi:10.1038/s41388-018-0391-0

Cited by 131 publications

(100 citation statements)

References 33 publications

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“…This involvement of Rab27A in pro-metastatic changes was confirmed when knock-down of Rab27A in melanoma mice models resulted in decreased metastasis formation in vivo [64]. In hepatocellular carcinoma, the uptake of exosomes from adherent hepatocellular carcinoma cells by detached cancer cells resulted in the release of adhesion-associated proteins and mRNA that induced the attachment of these cells, which was in turn associated with lung metastasis in vivo [65]. In ovarian cancer, injection of exosomes from highly metastatic cell lines in mice models resulted in increased ability to metastasise when compared with exosomes from low-metastatic-capacity cells [66].…”

Section: Induction Of Pro-metastatic Phenotypesmentioning

confidence: 77%

Exosomes in Bone Sarcomas: Key Players in Metastasis

Chicón-Bosch

Tirado

2020

Cells

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Bone sarcomas are rare cancers which often present with metastatic disease and are still associated with poor survival rates. Studies in the last decade have identified that exosomes, a type of extracellular vesicle released by cells, play an important role in tumour progression and dissemination. Through the transfer of their cargo (RNAs, proteins, and lipids) across cells, they are involved in cellular cross-talk and can induce changes in cellular behaviour. Exosomes have been shown to be important in metastasis organotropism, induction of angiogenesis and vascular permeability, the education of cells towards a pro-metastatic phenotype or the interaction between stromal and tumour cells. Due to the importance exosomes have in disease progression and the high incidence of metastasis in bone sarcomas, recent studies have evaluated the implications of these extracellular vesicles in bone sarcomas. In this review, we discuss the studies that evaluate the role of exosomes in osteosarcoma, Ewing sarcoma, and preliminary data on chondrosarcoma.

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Section: Induction Of Pro-metastatic Phenotypesmentioning

confidence: 77%

Exosomes in Bone Sarcomas: Key Players in Metastasis

Chicón-Bosch

Tirado

2020

Cells

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“…Some groups revealed that HCC promoted metastasis by secreting exosomes via the SMAD3 or the mitogen-activated protein kinase signaling pathway. 35,36 Exosomal miR-93 or miR-210 were found to influence migration, invasion, and angiogenesis of HCC. 37,38 In combination with our data, miR-296 exosome was released by HCC cells to act on HDLEC cells and then modulated lymphangiogenesis.…”

Section: Discussionmentioning

confidence: 99%

HANR promotes lymphangiogenesis of hepatocellular carcinoma via secreting miR‐296 exosome and regulating EAG1/VEGFA signaling in HDLEC cells

Shi

Yang

Sun

et al. 2019

J of Cellular Biochemistry

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The long noncoding RNA HANR has been shown to be involved in the progression of hepatocellular carcinoma (HCC). However, the underlying mechanism of HCC‐associated long noncoding RNA (HANR)–regulated HCC metastasis and lymphangiogenesis has not been elucidated. RT‐qPCR and Western blot methods were utilized to detect the gene expressions. Interaction of HANR with miR‐296 was predicted by a bioinformatic program and validated by a dual‐luciferase reporter assay. For the functional experiment, a transwell invasion assay was utilized to examine the invasion abilities of HepG2 and Huh‐7 cells. The lymphatic vessel formation assay was used to show the HCC‐associated lymphatic vessel formation ability of human dermal lymphatic endothelial cells (HDLEC). HANR was shown to directly bind to miR‐296, and miR‐296 downregulated HANR expression in HepG2 cells. Then, we observed that miR‐296 inhibitor transfection in shHANR HCC cells could promote lymphatic vessel formation and invasion of HDLEC cells compared with shHANR HCC cells. EAG1 or VEGFA overexpression in HDLEC cells rescued lymphatic vessel formation and invasion in HDLEC cells coincubated with the medium of HepG2 cells expressing shHANR or miR‐296 mimic. Ultimately, HANR knockdown and miR‐296 mimic led to a significant decrease in the EAG1 and VEGFA expression levels in HepG2 cells. Here, we reveal a novel molecular mechanism in which the HANR/miR‐296/EAG1/VEGF axis is responsible for the lymphangiogenesis of HCC cells. Our findings provide more insights into developing therapeutical or diagnostic methods by targeting HANR.

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“…For example, gastric cancer (GC)-derived exosomes promote tumor cell proliferation by activating phosphatidylinositol 3-kinase (PI3K)/Akt and mitogen-activated protein kinase (MAPK) / extracellular signal-regulated kinase (ERK) pathways (33). (HCC)-derived exosomes of primary hepatocellular carcinoma regulate the adhesion of HCC cells in circulation by transmitting SMAD family member 3 (SMAD3), thus promoting tumor metastasis (34). Exoskeletons derived from (HNSCC) in head and neck squamous cell carcinoma can promote angiogenesis by reprogramming receptor endothelial cells (34).…”

Section: Discussionmentioning

confidence: 99%

“…(HCC)-derived exosomes of primary hepatocellular carcinoma regulate the adhesion of HCC cells in circulation by transmitting SMAD family member 3 (SMAD3), thus promoting tumor metastasis (34). Exoskeletons derived from (HNSCC) in head and neck squamous cell carcinoma can promote angiogenesis by reprogramming receptor endothelial cells (34). In addition, exosomes were found in various body uids such as saliva, blood and urine (35,36).…”

Section: Discussionmentioning

confidence: 99%

Expression characteristics of exosomal long non-coding RNA in abdominal aortic aneurysm

Li¹,

Zhao²,

Wan³

et al. 2020

Preprint

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Background and objective:Abdominal aortic aneurysm(AAA) is one of the important causes of morbidity and mortality in middle-aged and elderly people. Although the understanding of the physiology and pathology of AAA has been improved, the potential molecular mechanism of AAA is still unclear. The existing evidence confirms that exosomal lncRNAs have a wide range of biological functions, and its regulatory disorders are related to the occurrence of diseases such as AAA, but the internal mechanism is not clear. The main purpose of this study is to screen the differentially expressed lncRNAs in exosomes between normal people and patients with AAA and to understand its internal mechanism.Materials and methods:The plasma of a healthy control group and patients with abdominal aortic aneurysm was collected, and the lncRNAs of exosomes were extracted and sequenced. Differential expression was assessed by DEseq using read counts as input and chosen according to the criteria of |log2(fold change)| > 1 and adjusted p-value < 0.05. Based on the Kyoto encyclopedia of genes and genomes (KEGG) and biological pathway and gene ontology (GO) functional enrichment analysis, the target genes were analyzed, and the correlation between lncRNA and target genes was analyzed.Result:We screened 45 species differentially expressed lncRNAs and found pathway significantly related to these genes, namely metabolic pathways, calcium signaling pathways and protein processing in endoplasmic reticulum and They play a significant and important role in the metabolic process and the cell signaling.Conclusion:There was significant difference in expression of exosomal lncRNAs between normal subjects and AAA patients. LncRNAs in exosomes regulate in the progress of AAA by activating metabolic pathway and calcium signaling pathway, but the specific mechanism is not clear and needs to be further explored.

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Primary tumor-derived exosomes facilitate metastasis by regulating adhesion of circulating tumor cells via SMAD3 in liver cancer

Cited by 131 publications

References 33 publications

Exosomes in Bone Sarcomas: Key Players in Metastasis

Exosomes in Bone Sarcomas: Key Players in Metastasis

HANR promotes lymphangiogenesis of hepatocellular carcinoma via secreting miR‐296 exosome and regulating EAG1/VEGFA signaling in HDLEC cells

Expression characteristics of exosomal long non-coding RNA in abdominal aortic aneurysm

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