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Extracellular vesicles from human liver stem cells inhibit tumor angiogenesis
Author(s) -
Lopatina Tatiana,
Grange Cristina,
Fonsato Valentina,
Tapparo Marta,
Brossa Alessia,
Fallo Sofia,
Pitino Adriana,
HerreraSanchez Maria Beatriz,
Kholia Sharad,
Camussi Giovanni,
Bussolati Benedetta
Publication year - 2018
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.31796
Subject(s) - angiogenesis , mesenchymal stem cell , in vivo , biology , microrna , in vitro , cancer research , microbiology and biotechnology , stem cell , microvesicles , matrigel , gene , biochemistry , genetics
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.