1. Extracellular vesicles from human liver stem cells inhibit tumor angiogenesis
- Author
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Lopatina, Tatiana, Grange, Cristina, Fonsato, Valentina, Tapparo, Marta, Brossa, Alessia, Fallo, Sofia, Pitino, Adriana, Herrera-Sanchez, Maria Beatriz, Kholia, Sharad, Camussi, Giovanni, and Bussolati, Benedetta
- Subjects
Cancer Research ,exosomes ,extracellular vesicles ,human liver stem cells ,microRNA ,renal tumor endothelial cells ,tumor angiogenesis ,Oncology ,Neovascularization, Pathologic ,Stem Cells ,Mice, SCID ,Xenograft Model Antitumor Assays ,Extracellular Vesicles ,Mice ,Liver ,Hepatocytes ,Animals ,Humans - Abstract
Human liver stem-like cells (HLSC) and derived extracellular vesicles (EVs) were previously shown to exhibit anti-tumor activity. In our study, we investigated whether HLSC-derived EVs (HLSC-EVs) were able to inhibit tumor angiogenesis in vitro and in vivo, in comparison with EVs derived from mesenchymal stem cells (MSC-EVs). The results obtained indicated that HLSC-EVs, but not MSC-EVs, inhibited the angiogenic properties of tumor-derived endothelial cells (TEC) both in vitro and in vivo in a model of subcutaneous implantation in Matrigel. Treatment of TEC with HLSC-EVs led to the down-regulation of pro-angiogenic genes. Since HLSC-EVs carry a specific set of microRNAs (miRNAs) that could target these genes, we investigated their potential role by transfecting TEC with HLSC-EV specific miRNAs. We observed that four miRNAs, namely miR-15a, miR-181b, miR-320c and miR-874, significantly inhibited the angiogenic properties of TEC in vitro, and decreased the expression of some predicted target genes (ITGB3, FGF1, EPHB4 and PLAU). In parallel, TEC treated with HLSC-EVs significantly enhanced expression of miR-15a, miR-181b, miR-320c and miR-874 associated with the down-regulation of FGF1 and PLAU. In summary, HLSC-EVs possess an anti-tumorigenic effect, based on their ability to inhibit tumor angiogenesis.
- Published
- 2018