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Protein & Cell ; (12): 932-941, 2013.
Article Dans Anglais | WPRIM | ID: wpr-757549

Résumé

Tumor-associated macrophages (TAMs) mostly exhibit M2-like (alternatively activated) properties and play positive roles in angiogenesis and tumorigenesis. Vascular endothelial growth factor (VEGF) is a key angiogenic factor. During tumor development, TAMs secrete VEGF and other factors to promote angiogenesis; thus, anti-treatment against TAMs and VEGF can repress cancer development, which has been demonstrated in clinical trials and on an experimental level. In the present work, we show that miR-150 is an oncomir because of its promotional effect on VEGF. MiR-150 targets TAMs to up-regulate their secretion of VEGF in vitro. With the utilization of cell-derived vesicles, named microvesicles (MVs), we transferred antisense RNA targeted to miR-150 into mice and found that the neutralization of miR-150 down-regulates miR-150 and VEGF levels in vivo and attenuates angiogenesis. Therefore, we proposed the therapeutic potential of neutralizing miR-150 to treat cancer and demonstrated a novel, natural, microvesicle-based method for the transfer of nucleic acids.


Sujets)
Animaux , Humains , Mâle , Souris , Carcinogenèse , Génétique , Métabolisme , Anatomopathologie , Lignée cellulaire tumorale , Exosomes , Cellules HEK293 , Hétérogreffes , Macrophages , Métabolisme , Souris de lignée C57BL , microARN , Génétique , Métabolisme , Transplantation tumorale , ARN antisens , Génétique , Régulation positive , Facteur de croissance endothéliale vasculaire de type A , Génétique , Métabolisme
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