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Neuroblastoma-secreted exosomes carrying miR-375 promote osteogenic differentiation of bone-marrow mesenchymal stromal cells. 2020
Marta Colletti, and
Luigi Tomao, and
Angela Galardi, and
Alessandro Paolini, and
Virginia Di Paolo, and
Cristiano De Stefanis, and
Paolo Mascio, and
Francesca Nazio, and
Stefania Petrini, and
Aurora Castellano, and
Ida Russo, and
Roberta Caruso, and
Simone Piga, and
Rita De Vito, and
Luisa Pascucci, and
Hector Peinado, and
Andrea Masotti, and
Franco Locatelli, and
Angela Di Giannatale
Department of Pediatric Onco-Hematology and Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
Bone marrow (BM) is the major target organ for neuroblastoma (NB) metastasis and its involvement is associated with poor outcome. Yet, the mechanism by which NB cells invade BM is largely unknown. Tumour microenvironment represents a key element in tumour progression and mesenchymal stromal cells (MSCs) have been recognized as a fundamental part of the associated tumour stroma. Here, we show that BM-MSCs isolated from NB patients with BM involvement exhibit a greater osteogenic potential than MSCs from non-infiltrated BM. We show that BM metastasis-derived NB-cell lines secrete higher levels of exosomal miR-375, which promotes osteogenic differentiation in MSCs. Of note, clinical data demonstrate that high level of miR-375 correlates with BM metastasis in NB patients. Our findings suggest, indeed, a potential role for exosomal miR-375 in determining a favourable microenvironment in BM to promote metastatic progression. MiR-375 may, thus, represent a novel biomarker and a potential target for NB patients with BM involvement.
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