Exosomal transfer of miR-126 promotes the anti-tumour response in malignant mesothelioma: Role of miR-126 in cancer-stroma communication

0521316 - BTÚ 2020 RIV NL eng J - Journal Article
Monaco, F. - Gaetani, S. - Alessandrini, F. - Tagliabracci, A. - Bracci, M. - Valentino, M. - Neužil, Jiří - Amati, M. - Bovenzi, M. - Tomasetti, M. - Santarelli, L.
Exosomal transfer of miR-126 promotes the anti-tumour response in malignant mesothelioma: Role of miR-126 in cancer-stroma communication.
Cancer letters. Roč. 463, č. 2019 (2019), s. 27-36. ISSN 0304-3835. E-ISSN 1872-7980
R&D Projects: GA MZd(CZ) NV16-31604A
Institutional support: RVO:86652036
Keywords : pleural mesothelioma * angiogenesis * cells * repression * apoptosis
OECD category: Oncology
Impact factor: 7.360, year: 2019
Method of publishing: Open access
https://www.sciencedirect.com/science/article/abs/pii/S0304383519304240?via%3Dihub

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.
Permanent Link: http://hdl.handle.net/11104/0305953