Exosomal transfer of miR-126 promotes the anti-tumour response in malignant mesothelioma: Role of miR-126 in cancer-stroma communication
| Autor: | Massimo Bovenzi, Lory Santarelli, Matteo Valentino, Federica Monaco, Jiri Neuzil, Marco Tomasetti, Massimo Bracci, Monica Amati, Adriano Tagliabracci, Simona Gaetani, Federica Alessandrini |
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| Přispěvatelé: | Monaco, Federica, Gaetani, Simona, Alessandrini, Federica, Tagliabracci, Adriano, Bracci, Massimo, Valentino, Matteo, Neuzil, Jiri, Amati, Monica, Bovenzi, Massimo, Tomasetti, Marco, Santarelli, Lory |
| Rok vydání: | 2019 |
| Předmět: |
Mesothelioma
Vascular Endothelial Growth Factor A 0301 basic medicine EGF Family of Proteins Cancer Research Cell signaling Lung Neoplasms Stromal cell miRNA-based therapy Carcinogenesis Angiogenesis Cell Communication Exosomes 03 medical and health sciences 0302 clinical medicine Stroma Humans Malignant mesothelioma Cells Cultured Tube formation Cell growth Chemistry Calcium-Binding Proteins Mesothelioma Malignant miR-126 Fibroblasts Cancer stroma Microvesicles Exosome MicroRNAs 030104 developmental biology Oncology 030220 oncology & carcinogenesis Cancer research EGFL7 Signal Transduction |
| Zdroj: | Cancer Letters. 463:27-36 |
| ISSN: | 0304-3835 |
| Popis: | MiR-126 has been shown to suppress malignant mesothelioma (MM) by targeting cancer-related genes without inducing toxicity or histopathological changes. Exosomes provide the opportunity to deliver therapeutic cargo to cancer stroma. Here, a tumour stromal model composed of endothelial cells (HUVECs), fibroblasts (IMR-90 cells), non-malignant mesothelial cells (Met-5A cells) and MM cells (H28 and MM-B1 cells) was used. The cells were treated with exosomes from HUVECs carrying endogenous (exo-HUVEC) and enriched miR-126 (exo-HUVECmiR−126), and the uptake/turnover of exosomes; miR-126 distribution within the stroma; and effect of miR-126 on cell signalling, angiogenesis and cell proliferation were evaluated. Based on the sensitivity of MM cells to exo-HUVEC miR-126 treatment, miR-126 was distributed differently across stromal cells. The reduced miR-126 content in fibroblasts in favour of endothelial cells reduced angiogenesis and suppressed cell growth in an miR-126-sensitive environment. Conversely, the accumulation of miR-126 in fibroblasts and the reduced level of miR-126 in endothelial cells induced tube formation in an miR-126-resistant environment via VEGF/EGFL7 upregulation and IRS1-mediated cell proliferation. These findings suggest that transfer of miR-126 via HUVEC-derived exosomes represents a novel strategy to inhibit angiogenesis and cell growth in MM. |
| Databáze: | OpenAIRE |
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