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Topics {✒️}

mtor/hif-1α/vegf signaling axis mtor/hif-1α signaling axis egf/egfr/akt pathway bone marrow-derived cells nf-kappab activity decreases hypoxia-inducible factor 1alpha breast cancer-derived cells mtorc1 drives hif-1alpha human bone marrow platelet-activating factor synthesis month download article/chapter hypoxia-induced pulmonary hypertension exosome-mediated transfer enzyme-linked immunosorbent assay acute ischemia/reperfusion injury internally expressed vegfr1/flt1 mesenchymal stem cells breast tumour angiogenesis msc-derived exosomes induce breast cancer stem hypoxia-inducible factor 1 serum-derived extracellular vesicles microrna-100 promotes migration endothelial cell proliferation real-time quantitative pcr book  google scholar human breast carcinoma breast cancer cells mesenchymal tumor cells seyed javad mowla microrna-140-5p inhibits invasion breast cancer metastasis suppress tumor growth springer international publishing full article pdf majid mossahebi-mohammadi related subjects tumour suppressive roles mtor signaling motif anti-proliferative activity stem cell biology check access instant access stem cell sciences privacy choices/manage cookies author information authors modulate vascular responses mtor signalling pathway secreted vegf protein cardiovascular research institute

Questions {❓}

• Marini 3rd, Concise review: Dissecting a discrepancy in the literature: Do mesenchymal stem cells support or suppress tumor growth?
• Tagliaferri, mTOR inhibitors, a new era for metastatic luminal HER2-negative breast cancer?

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         headline:MicroRNA-100 shuttled by mesenchymal stem cell-derived exosomes suppresses in vitro angiogenesis through modulating the mTOR/HIF-1α/VEGF signaling axis in breast cancer cells
         description:Human mesenchymal stem cells (MSCs) have been shown to be involved in the formation and modulation of tumor stroma and in interacting with tumor cells, partly through their secretome. Exosomes are nano-sized intraluminal multi-vesicular bodies secreted by most types of cells and have been found to mediate intercellular communication through the transfer of genetic information via coding and non-coding RNAs to recipient cells. Since exosomes are considered as protective and enriched sources of shuttle microRNAs (miRNAs), we hypothesized that exosomal transfer of miRNAs from MSCs may affect tumor cell behavior, particularly angiogenesis. Exosomes derived from MSCs were isolated and characterized by scanning electron microscopy analyses, dynamic light scattering measurements, and Western blotting. Fold changes in miR-100 expression levels were calculated in exosomes and their corresponding donor cells by qRT-PCR. The effects of exosomal transfer of miR-100 from MSCs were assessed by qRT-PCR and Western blotting of the mTOR/HIF-1α/VEGF signaling axis in breast cancer cells. The quantification of secreted VEGF protein was determined by enzyme-linked immunosorbent assay. The putative paracrine effects of MSC-derived exosomes on tumor angiogenesis were explored by in vitro angiogenesis assays including endothelial cell proliferation, migration and tube formation assays. We found that MSC-derived exosomes induce a significant and dose-dependent decrease in the expression and secretion of vascular endothelial growth factor (VEGF) through modulating the mTOR/HIF-1α signaling axis in breast cancer-derived cells. We also found that miR-100 is enriched in MSC-derived exosomes and that its transfer to breast cancer-derived cells is associated with the down-regulation of VEGF in a time-dependent manner. The putative role of exosomal miR-100 transfer in regulating VEGF expression was substantiated by the ability of anti-miR-100 to rescue the inhibitory effects of MSC-derived exosomes on the expression of VEGF in breast cancer-derived cells. In addition, we found that down-regulation of VEGF mediated by MSC-derived exosomes can affect the vascular behavior of endothelial cells in vitro. Overall, our findings suggest that exosomal transfer of miR-100 may be a novel mechanism underlying the paracrine effects of MSC-derived exosomes and may provide a means by which these vesicles can modulate vascular responses within the microenvironment of breast cancer cells.
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      headline:MicroRNA-100 shuttled by mesenchymal stem cell-derived exosomes suppresses in vitro angiogenesis through modulating the mTOR/HIF-1α/VEGF signaling axis in breast cancer cells
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         Exosome
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