Exosomes derived from colon cancer cells and plasma of colon cancer patients promote migration of SW480 cells through Akt/mTOR pathway

Pang, Honglin; Liu, Lei; Sun, Xiaobin; Xi, Weidong; Bao, Yu; Wu, Liping; Shan, Jing; Wang, Zhiming; Guo, Yuanbiao; Zhao, Cong

doi:10.1016/j.prp.2021.153454

Cited by 11 publications

(13 citation statements)

References 41 publications

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“…In our study, the primary cultured human PMSCs were positive for predominant markers (CD73, CD90, and CD105), which was consistent with previous study [ 40 ], indicating obtained PMSCs with high purity and uniformity. Subsequently, TEM and NTA results revealed that PMSC-Exos possess the characteristics of exosomes and accounted for 99% of the total, which was parallel with previous studies [ 41 ], suggesting successful isolation of human PMSC-Exos. In the present study, we hypothesized that PMSC-Exos may represent a novel alternative treatment in MI.…”

Section: Discussionsupporting

confidence: 85%

Exosomes derived from human placental mesenchymal stem cells ameliorate myocardial infarction via anti-inflammation and restoring gut dysbiosis

Yang

Wang

Zhang

et al. 2022

BMC Cardiovasc Disord

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Background Myocardial infarction (MI) represents a severe cardiovascular disease with limited therapeutic agents. This study was aimed to elucidate the role of the exosomes derived from human placental mesenchymal stem cells (PMSCs-Exos) in MI. Methods PMSCs were isolated and cultured in vitro, with identification by both transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). To further investigate the effects of PMSC-Exos on MI, C57BL/6 mice were randomly divided into Sham group, MI group, and PMSC-Exos group. After 4 weeks of the intervention, cardiac function was assessed by cardiac echocardiography, electrocardiogram and masson trichrome staining; lipid indicators were determined by automatic biochemical instrument; inflammatory cytokines were measured by cytometric bead array (CBA); gut microbiota, microbial metabolites short chain fatty acids (SCFAs) as well as lipopolysaccharide (LPS) were separately investigated by 16S rRNA high throughput sequencing, gas chromatography mass spectrometry (GC–MS) and tachypleus amebocyte lysate kit; transcriptome analysis was used to test the transcriptional components (mRNA\miRNA\cirRNA\lncRNA) of PMSC-Exos. Results We found that human PMSC-Exos were obtained and identified with high purity and uniformity. MI model was successfully established. Compared to MI group, PMSC-Exos treatment ameliorated myocardial fibrosis and left ventricular (LV) remodeling (P < 0.05). Moreover, PMSC-Exos treatment obviously decreased MI molecular markers (AST/BNP/MYO/Tn-I/TC), pro-inflammatory indicators (IL-1β, IL-6, TNF-α, MCP-1), as well as increased HDL in comparison with MI group (all P < 0.05). Intriguingly, PMSC-Exos intervention notably modulated gut microbial community via increasing the relative abundances of Bacteroidetes, Proteobacteria, Verrucomicrobia, Actinobacteria, Akkermansia, Bacteroides, Bifidobacterium, Thauera and Ruminiclostridium, as well as decreasing Firmicutes (all P < 0.05), compared with MI group. Furthermore, PMSC-Exos supplementation increased gut microbiota metabolites SCFAs (butyric acid, isobutyric acid and valeric acid) and decreased LPS in comparison with MI group (all P < 0.05). Correlation analysis indicated close correlations among gut microbiota, microbial SCFAs and inflammation in MI. Conclusions Our study highlighted that PMSC-Exos intervention alleviated MI via modulating gut microbiota and suppressing inflammation.

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Section: Discussionsupporting

confidence: 85%

Exosomes derived from human placental mesenchymal stem cells ameliorate myocardial infarction via anti-inflammation and restoring gut dysbiosis

Yang

Wang

Zhang

et al. 2022

BMC Cardiovasc Disord

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“…SW620 cells have a more rounded shape and strong plasma membrane blebbing activity (see above Figure 1 A,D), which is associated with amoeboid motility [ 68 ]. Since these morphological traits can be transferred to SW480 cells via EVs derived from SW620 cells and influence their motility [ 8 , 9 , 10 , 51 ], we evaluated their migration and the impact of CD9 Abs. For this purpose, we used two classical methods: the linear wound healing assay and the Transwell filter assay (see Section 2 ).…”

Section: Resultsmentioning

confidence: 99%

“…This pathway and possibly others, including those that involve the nuclear transfer of EV content (see below) [ 57 ], could explain the morphological transformation of SW480 cells. The Akt/mTOR pathway could also be involved [ 51 ].…”

Section: Discussionmentioning

confidence: 99%

“…Here, we investigated whether this approach could have therapeutic utility for intercepting the EV-mediated transformation of colon carcinoma. To this aim, we used the established isogenic cell line model of non-metastatic SW480 cells and highly metastatic SW620 cells, where EVs derived from the latter can transform the former and impact their malignant properties, including their motility [ 10 , 51 ]. These cell lines were derived from primary (i.e., SW480 cells) and secondary (SW620 cells) tumors from a single patient [ 52 , 53 , 54 ].…”

Section: Introductionmentioning

confidence: 99%

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Anti-Human CD9 Fab Fragment Antibody Blocks the Extracellular Vesicle-Mediated Increase in Malignancy of Colon Cancer Cells

Santos

Rappa

Fontana

et al. 2022

Cells

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Intercellular communication between cancer cells themselves or with healthy cells in the tumor microenvironment and/or pre-metastatic sites plays an important role in cancer progression and metastasis. In addition to ligand–receptor signaling complexes, extracellular vesicles (EVs) are emerging as novel mediators of intercellular communication both in tissue homeostasis and in diseases such as cancer. EV-mediated transfer of molecular activities impacting morphological features and cell motility from highly metastatic SW620 cells to non-metastatic SW480 cells is a good in vitro example to illustrate the increased malignancy of colorectal cancer leading to its transformation and aggressive behavior. In an attempt to intercept the intercellular communication promoted by EVs, we recently developed a monovalent Fab fragment antibody directed against human CD9 tetraspanin and showed its effectiveness in blocking the internalization of melanoma cell-derived EVs and the nuclear transfer of their cargo proteins into recipient cells. Here, we employed the SW480/SW620 model to investigate the anti-cancer potential of the anti-CD9 Fab antibody. We first demonstrated that most EVs derived from SW620 cells contain CD9, making them potential targets. We then found that the anti-CD9 Fab antibody, but not the corresponding divalent antibody, prevented internalization of EVs from SW620 cells into SW480 cells, thereby inhibiting their phenotypic transformation, i.e., the change from a mesenchymal-like morphology to a rounded amoeboid-like shape with membrane blebbing, and thus preventing increased cell migration. Intercepting EV-mediated intercellular communication in the tumor niche with an anti-CD9 Fab antibody, combined with direct targeting of cancer cells, could lead to the development of new anti-cancer therapeutic strategies.

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“…In the meantime, it was proved that diabetes altered the activation of AKT pathway negatively, leading to decreased proliferation and delayed wound healing [ 38 ]. There also be some evidence that exosome could regulate AKT pathway for adjusting cell functions [ 39 ]. Based on these, the healing effect of ADSC-exo on diabetic wounds might be regulated by AKT pathway.…”

Section: Introductionmentioning

confidence: 99%

ADSC-exo@MMP-PEG smart hydrogel promotes diabetic wound healing by optimizing cellular functions and relieving oxidative stress

Jiang

Liu

et al. 2022

Materials Today Bio

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Exosomes derived from colon cancer cells and plasma of colon cancer patients promote migration of SW480 cells through Akt/mTOR pathway

Cited by 11 publications

References 41 publications

Exosomes derived from human placental mesenchymal stem cells ameliorate myocardial infarction via anti-inflammation and restoring gut dysbiosis

Exosomes derived from human placental mesenchymal stem cells ameliorate myocardial infarction via anti-inflammation and restoring gut dysbiosis

Anti-Human CD9 Fab Fragment Antibody Blocks the Extracellular Vesicle-Mediated Increase in Malignancy of Colon Cancer Cells

ADSC-exo@MMP-PEG smart hydrogel promotes diabetic wound healing by optimizing cellular functions and relieving oxidative stress

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