Force-feeding malignant mesothelioma stem-cell like with exosome-delivered miR-126 induces tumour cell killing

• DOI: 10.1016/j.tranon.2022.101400
• Publication Date: 2022-03-23T03:50:57Z
• Authors: Federica Monaco; Laura De Conti; Simone Vodret; Nunzia Zanotta; Manola Comar; Sandra Manzotti; Corrado Rubini; Laura Graciotti; Gianluca Fulgenzi; Massimo Bovenzi; Marco Baralle; Marco Tomasetti; Lory Santarelli
• Keywords: Exosome

Malignant pleural mesothelioma (MPM) is an aggressive tumour resistant to treatments. It has been postulated that cancer stem cells (CSCs) persist in tumours causing relapse after multimodality treatment. In the present study, a novel miRNA-based therapy approach proposed. MPM-derived spheroids have treated with exosome-delivered miR-126 (exo-miR) and evaluated for their anticancer effect. The exo-miR treatment increased MPM stem-cell like stemness inhibited cell proliferation. However, at prolonged time, up taken was released by themselves through exosomes; inhibition of exosome release inhibitor GW4869 induced intracellular accumulation leading massive death vivo growth arrest. Autophagy involved these processes; protective autophagy this process generates metabolic crisis promotes necroptosis, which associated PARP-1 over-expression cyt-c AIF release. Here, first we proposed against CSCs, heterogeneous population development relapse.