Communication in tiny packages: Exosomes as means of tumor-stroma communication

Daßler-Plenker, Juliane; Küttner, Victoria; Egeblad, Mikala

doi:10.1016/j.bbcan.2020.188340

Cited by 54 publications

(46 citation statements)

References 164 publications

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“…Tumor-derived exosomes are transmission vesicles mediating intercellular communications and participating in multiple cancer procedures, such as tumor microenvironment remodeling, immune response, angiogenesis, invasion, metastasis and drug-resistance [8]. Although GC-derived exosomes have been largely studied since the first characterization decades ago [20], the publications on the regulation of GC angiogenesis are limited.…”

Section: Discussionmentioning

confidence: 99%

“…In the past decade, studies for angiogenesis have focused on the intercellular communications, with exosomes as the important mediators [7,8]. Exosomes are nanoscale extracellular vesicles that could be secreted by almost all types of cells and contain variety of biomolecules, such as mRNA and proteins [8,9]. According to the in-vitro and in-vivo studies, exosomes derived from cancer cells are supposed to mediate vascular formations [7,8].…”

Section: Introductionmentioning

confidence: 99%

“…Exosomes are nanoscale extracellular vesicles that could be secreted by almost all types of cells and contain variety of biomolecules, such as mRNA and proteins [8,9]. According to the in-vitro and in-vivo studies, exosomes derived from cancer cells are supposed to mediate vascular formations [7,8]. Furthermore, exosomes were demonstrated to transfer angiogenic stimulatory molecules to neovasculature related cells, or involve in the reprogramming and modulation of endothelial cells by inducing the expression of pro-angiogenesis genes [10,11].…”

Section: Introductionmentioning

confidence: 99%

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YB-1 transferred by gastric cancer exosomes promotes angiogenesis via enhancing the expression of angiogenic factors in vascular endothelial cells

Xue

Huang

et al. 2020

BMC Cancer

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Background Angiogenesis is important for the progression of gastric cancer (GC). Y-box binding protein 1 (YB-1) predicts advanced disease and indicates neovasculature formation in GC tissues, while the related mechanisms remain elusive. Exosomes mediate intercellular communications via transferring various molecules including proteins, lipids, mRNAs, and microRNAs, while the cargos of GC exosomes and the related mechanisms in GC angiogenesis were rarely reported except for several microRNAs. Methods In this study, human umbilical vein endothelial cells (HUVECs) were, respectively, treated by the exosomes isolated from the YB-1 transfected and the control SGC-7901 cells (SGC-7901-OE-Exo and SGC-7901-NC-Exo), and their apoptosis, proliferation, migration, invasion, and angiogenesis were, sequentially, compared. The levels of angiogenic factors including VEGF, Ang-1, MMP-9 and IL-8 in the exosome-treated HUVECs and the GC-derived exosomes were, separately, detected using PCR and Western blotting as well as RNA sequencing assays. Results We observed the consistent level of YB-1 in the exosomes and their originated GC cells, and the internalization of exosomes into HUVECs. Comparing with SGC-7901-NC-Exo, SGC-7901-OE-Exo significantly inhibited the apoptosis but promoted the proliferation, migration, invasion, and angiogenesis of HUVECs, within which the increased mRNA and protein levels of VEGF, Ang-1, MMP-9 and IL-8 were demonstrated. Meanwhile, mRNA levels of VEGF, Ang-1, MMP-9 and IL-8 showed no significant difference between SGC-7901-NC-Exo and SGC-7901-OE-Exo, although statistically higher mRNA of YB-1 was detected in the SGC-7901-OE-Exo. Conclusions Our findings illustrate YB-1 as the key component of exosome to promote GC angiogenesis by upregulating specific angiogenic factors in the exosome-treated endothelial cells but not in the exosomes themselves.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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YB-1 transferred by gastric cancer exosomes promotes angiogenesis via enhancing the expression of angiogenic factors in vascular endothelial cells

Xue

Huang

et al. 2020

BMC Cancer

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“…Much evidence exists for the important role of these vesicles in intercellular communications and their involvement with both pathological and physiological conditions [13,14]. Exosomes have also been implicated in intracellular communication, angiogenesis, immune system modulation and metastasis progression in cancer [15][16][17][18]. The techniques used to isolate and enrich exosomes from biological samples include precipitationultracentrifugation and ultracentrifugation followed by differential gradient centrifugation [6,[19][20][21].…”

Section: Introductionmentioning

confidence: 99%

Exosomal microRNAs derived from mesenchymal stem cells: cell-to-cell messages

et al. 2020

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Exosomes are extracellular vesicles characterized by their size, source, release mechanism and contents. MicroRNAs (miRNAs) are single stranded non-coding RNAs transcribed from DNA. Exosomes and miRNAs are widespread in eukaryotic cells, especially in mesenchymal stem cells (MSCs). MSCs are used for tissue regeneration, and also exert paracrine, anti-inflammatory and immunomodulatory effects. However, the use of MSCs is controversial, especially in the presence or after the remission of a tumor, due to their secretion of growth factors and their migration ability. Instead of intact MSCs, MSC-derived compartments or substances could be used as practical tools for diagnosis, follow up, management and monitoring of diseases. Herein, we discuss some aspects of exosomal miRNAs derived from MSCs in the progression, diagnosis and treatment of various diseases.

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“…It is shown that once exosomes are released, the next step is the uptake of their contents by the recipient cells, and some exosomes-induced cellular responses do not require the recipient cells to absorb the exosomes. Signal cellular communication can be caused by adhesion of exosomes surface proteins to receptors expressed on the recipient cells (Dassler-Plenker et al, 2020). Therefore, HK-2-derived exosomes were extracted and applied to the HMC proliferation model to observe the direct effect.…”

Section: Discussionmentioning

confidence: 99%

Zhen-Wu-Tang Protects IgA Nephropathy in Rats by Regulating Exosomes to Inhibit NF-κB/NLRP3 Pathway

et al. 2020

Front. Pharmacol.

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Immunoglobulin A nephropathy (IgAN) is one of the most frequent kinds of primary glomerulonephritis characterized by IgA immune complexes deposition and glomerular proliferation. Zhen-wu-tang (ZWT), a well-known traditional Chinese formula has been reported to ameliorate various kidney diseases. However, its pharmacological mechanism remains unclear. Exosomes have been described in diverse renal diseases by mediating cellular communication but rarely in the IgAN. The purpose of the present study is to explore whether the underlying mechanisms of the effect of ZWT on IgAN is correlated to exosomes. Our results demonstrated that in human renal tubular epithelial cells (HK-2) stimulated by lipopolysaccharide, exosomes are obviously released after ZWT-containing serum treatment especially with 10% ZWT. In addition, once released, HK-2-derived exosomes were uptaked by human mesangial cells (HMC), which impeded the activation of NF-kB/NLRP3 signaling pathway to exert anti-inflammatory effects in a lipopolysaccharide induced proliferation model. Moreover, IgAN rat model was established by bovine serum albumin, CCL 4 mixed solution and LPS. We found that 10% ZWT could significantly promote the release of exosomes from HK-2 and inhibit HMC proliferation to improve inflammation. Thus HK-2-derived exosomes treated with 10% ZWT (ZWT-EXO) were administered to the rats by tail vein injection. Our results showed that ZWT-EXO decreased the levels of 24 h proteinuria, urinary erythrocyte, IgA deposition in glomerulus and renal pathological injury which ameliorated the kidney damage. In addition, ZWT was able to dramatically promote secretion of exosomes in renal tissues while blocked NF-kB nuclear translocation as well as activation of NLRP3 inflammasome, leading to the inhibition of IL-1b and caspase-1. In conclusion, our study reveal that ZWT has protective effects on IgAN by regulating exosomes secretion to inhibit the activation of NF-kB/NLRP3 pathway, thereby attenuating the renal dysfunction. These findings may provide a new therapeutic target for the treatment of IgAN.

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Communication in tiny packages: Exosomes as means of tumor-stroma communication

Cited by 54 publications

References 164 publications

YB-1 transferred by gastric cancer exosomes promotes angiogenesis via enhancing the expression of angiogenic factors in vascular endothelial cells

YB-1 transferred by gastric cancer exosomes promotes angiogenesis via enhancing the expression of angiogenic factors in vascular endothelial cells

Exosomal microRNAs derived from mesenchymal stem cells: cell-to-cell messages

Zhen-Wu-Tang Protects IgA Nephropathy in Rats by Regulating Exosomes to Inhibit NF-κB/NLRP3 Pathway

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